Researchers Announce a Breakthrough on HIV/AIDS Treatment
A technique that alters T cells has been shown to reduce the amount of virus in infected people.
By Deborah Erickson
For the first time, researchers have shown that a cell-based therapy for HIV/AIDS can reduce the amount of virus in infected people. The breakthrough — big news for researchers, who have struggled for decades to create vaccines and cell-based therapies for HIV — was announced on Sunday at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago. To date, the sole treatment for HIV has been multidrug regimens that prolong life but never eliminate the virus.
Sangamo BioSciences of Richmond, California, says it has found a way to protect the T cells that HIV attacks first, so they can live to fight another day. The approach entails temporarily stopping a patient’s antiretroviral therapy and removing T cells carrying the CD4 receptor. This surface protein is the doorway by which the virus gains entry into the cell. The collected T cells are exposed to zinc finger nuclease, an enzyme designed to remove the gene for a coreceptor of CD4 called CCR5. The cells are then reinfused into the patient. Once they’re back in the body, the new study shows, the cells persist and travel in the body just like normal T cells.
Sangamo’s approach is based on the observation that some people have a naturally occurring mutation in the CCR5 gene that protects them against HIV. Ordinarily, humans have two copies of every gene. It turns out that individuals with a mutation in both copies of the CCR5 gene cannot be infected by the most common HIV strains. In people with the so-called Delta-32 mutation in just one copy of the gene, infection rarely progresses to AIDS. In the U.S., about 1 percent of the population is thought to carry the helpful mutation, which some researchers believe arose as protection against the Black Death.
Previous evidence existed showing that CCR5-negative cells could help AIDS patients. In 2007, an American man with AIDS and lymphoma received, as treatment for the cancer, a bone-marrow transplant from a person with the CCR5 mutation. The marrow recipient has been free of both AIDS and cancer since then. Sangamo’s method treats a patient’s own cells, with less risk than a marrow transplant.
“The data are very encouraging,” says Edward Lanphier, Sangamo’s founding CEO. “We are seeing a statistically significant correlation between our treatment and viral load reduction. This is a big step forward toward our goal of developing a functional cure for the disease.” Lanphier envisions that someday AIDS patients will not need to be on aggressive antiretroviral therapies because their virus will be well-controlled—or even undetectable, as happened with one subject with a mutation in one CCR5 gene.
Experts unaffiliated with Sangamo and its clinical trials agree that the scientific achievement is impressive, but they question the notion that it could yield a functional cure. Gerhard Bauer, assistant professor in the Stem Cell Program at the University of California, Davis, and director of that school’s Good Manufacturing Practice laboratory at the Institute for Regenerative Cures, says, “this is a great move forward, to demonstrate reduction of viral load by pushing in modified T cells. It has never been done before by any company, and I congratulate them 100 percent.”
However, Bauer says, he is “not so sure” the company will be able to create a functional cure. T cells don’t live forever, he points out.
“This is encouraging,” says Ellen Feigal, vice president of R&D at the California Institute for Regenerative Medicine, “and it provides supporting evidence for a study we funded that would take the work to the next step.” This study, by researchers at City of Hope, a cancer center in Duarte, California, aims to provide patients with a permanent supply of HIV-resistant T cells. The strategy calls for modifying patients’ blood-forming stem cells, which produce all future T cells as well as the macrophages and dendritic cells that can also be HIV targets.
Sangamo is also exploring the potential of stem-cell modification with City of Hope researchers, but the company does not concede that modified stem cells will be necessary or any better than T cells. “Yes, T cells turn over,” says Geoff Nichol, who joined Sangamo as executive vice president of R&D a few months ago to commercialize the platform, “but there are some very long-lasting subsets that can live for years and years and remember the epitope they came up against. We are feeling bullish about T cells because of our data.”
Sangamo’s news is “certainly scientifically interesting,” observes Warner Greene, director of the Gladstone Institute at the University of California, San Francisco. But, he points out, no cell therapy, whether it involves T cells or stem cells, is a practical approach to treating HIV/AIDS throughout the developing world, where seven out of 10 new infections are occurring. “We really need to be looking for therapies that can benefit the millions of individuals with HIV, not just a select few who might be able to afford cellular therapies.”
Copyright TechnologyReview.Com 2011
Sunday, September 18, 2011
Tuesday, July 26, 2011
Kaletra Plus Selzentry Yields Faster Response And Better Immune Recovery Than Kaletra Plus Truvada (IAS 2011)
By Courtney McQueen and April Clayton
Preliminary results from a small 48 week clinical trial indicate that previously untreated HIV-positive adults taking Kaletra plus Selzentry have better immune recovery and faster virologic response compared to participants taking the more standard regimen of Kaletra plus Truvada.
Based on their results, the researchers recommended further research into treatment regimens that do not contain nucleoside reverse transcriptase inhibitors (NRTIs) – such as Truvada – which currently form the backbone of antiretroviral therapy. They also noted that longer trials with more participants would be needed to confirm the long-term safety and efficacy of non-NRTI-based regimens.
The results were presented last week at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2011).
Traditional combination antiretroviral therapy regimens consist of two NRTIs plus at least one additional anti-HIV drug from a different class. However, due to side effects associated with NRTIs and the fact that some patients cannot take them due to allergies or other conditions, researchers have begun exploring alternative “NRTI-sparing” regimens (see related AIDS Beacon news).
In this study, researchers examined the efficacy of the non-NRTI-based regimen of Kaletra (lopinavir/ritonavir) plus Selzentry (maraviroc) versus the more traditional regimen of Kaletra plus Truvada (emtricitabine/tenofovir). Truvada is a combination of two NRTIs, while Kaletra is a protease inhibitor and Selzentry is a CCR5 inhibitor, which is a relatively new type of antiretroviral.
The trial included 38 HIV-positive adults who had not previously been treated for HIV. Half the participants were randomly assigned to receive Kaletra plus Selzentry, and the other half were assigned to take Kaletra plus Truvada. The researchers then assessed participants’ CD4 (white blood cell) counts and viral loads (amount of HIV in the blood) at 4, 12, 24, 36, and 48 weeks after starting treatment.
Results showed that after 48 weeks, participants in the non-NRTI Kaletra plus Selzentry group had significantly higher increases in CD4 counts than participants in the Kaletra plus Truvada group. The average increase in CD4 count for the Kaletra/Selzentry group was 226 cells per microliter, compared to 125 cells per microliter in the Kaletra/Truvada group.
Additionally, most participants in the non-NRTI group (83 percent) achieved undetectable viral loads by week 12, compared to less than half of patients in the Truvada group. By 48 weeks, 95 percent of participants in the Kaletra/Selzentry group had undetectable viral loads, compared to 83 percent of participants in the Kaletra/Truvada group.
The researchers also noted that three participants taking Kaletra plus Truvada had to interrupt treatment due to diarrhea. Overall one person in the Kaletra/Truvada group discontinued treatment, compared to none in the Kaletra/Selzentry group.
For more information, please see the study abstract and presentation (pdf) on the IAS 2011 conference website.
Copyright © 2011 AidsBeacon.com
By Courtney McQueen and April Clayton
Preliminary results from a small 48 week clinical trial indicate that previously untreated HIV-positive adults taking Kaletra plus Selzentry have better immune recovery and faster virologic response compared to participants taking the more standard regimen of Kaletra plus Truvada.
Based on their results, the researchers recommended further research into treatment regimens that do not contain nucleoside reverse transcriptase inhibitors (NRTIs) – such as Truvada – which currently form the backbone of antiretroviral therapy. They also noted that longer trials with more participants would be needed to confirm the long-term safety and efficacy of non-NRTI-based regimens.
The results were presented last week at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2011).
Traditional combination antiretroviral therapy regimens consist of two NRTIs plus at least one additional anti-HIV drug from a different class. However, due to side effects associated with NRTIs and the fact that some patients cannot take them due to allergies or other conditions, researchers have begun exploring alternative “NRTI-sparing” regimens (see related AIDS Beacon news).
In this study, researchers examined the efficacy of the non-NRTI-based regimen of Kaletra (lopinavir/ritonavir) plus Selzentry (maraviroc) versus the more traditional regimen of Kaletra plus Truvada (emtricitabine/tenofovir). Truvada is a combination of two NRTIs, while Kaletra is a protease inhibitor and Selzentry is a CCR5 inhibitor, which is a relatively new type of antiretroviral.
The trial included 38 HIV-positive adults who had not previously been treated for HIV. Half the participants were randomly assigned to receive Kaletra plus Selzentry, and the other half were assigned to take Kaletra plus Truvada. The researchers then assessed participants’ CD4 (white blood cell) counts and viral loads (amount of HIV in the blood) at 4, 12, 24, 36, and 48 weeks after starting treatment.
Results showed that after 48 weeks, participants in the non-NRTI Kaletra plus Selzentry group had significantly higher increases in CD4 counts than participants in the Kaletra plus Truvada group. The average increase in CD4 count for the Kaletra/Selzentry group was 226 cells per microliter, compared to 125 cells per microliter in the Kaletra/Truvada group.
Additionally, most participants in the non-NRTI group (83 percent) achieved undetectable viral loads by week 12, compared to less than half of patients in the Truvada group. By 48 weeks, 95 percent of participants in the Kaletra/Selzentry group had undetectable viral loads, compared to 83 percent of participants in the Kaletra/Truvada group.
The researchers also noted that three participants taking Kaletra plus Truvada had to interrupt treatment due to diarrhea. Overall one person in the Kaletra/Truvada group discontinued treatment, compared to none in the Kaletra/Selzentry group.
For more information, please see the study abstract and presentation (pdf) on the IAS 2011 conference website.
Copyright © 2011 AidsBeacon.com
Monday, July 25, 2011
NanoViricides announces anti-HIV therapy could lead to functional cure
by Deborah Sterescu
NanoViricides (OTCBB:NNVC) reported Monday that its lead anti-HIV candidate achieved an efficacy level equivalent to a highly active anti-retroviral triple (HAART) drug cocktail in a recent animal study.
Treatment with the drug reduced HIV levels and protected human immune T-cells to the same extent as treatment with the cocktail did in a study of mice, said the company. The three drug-combination used for comparison is one of the current therapies recommended for patients with HIV.
NanoViricides, which uses special purpose nanomaterials to design viral therapies, also said that no evidence of drug toxicity was observed during the study, and that the investigational drug will now undergo further optimization.
The latest study verifies the company’s previous results, which found that nanoviricides had a significant therapeutic effect, equal or superior to the same three-drug cocktail in a mouse study.
The company’s nanoviricide therapy works to mimick cellular structures to which the virus binds, specifically attacking and dismantling them. By working differently than many combination therapies, the drug developer believes that the nanoviral treatment, or HIVCide, could compliment current standard-of-care, possibly achieving a “functional cure” of HIV/AIDS, NanoViricides said.
Although a functional cure is not a complete cure, it would allow an infected person to continue normal life even after discontinuation of therapy, maintaining undetectable viral load until a recurrence.
“Creating an adjunct drug that acts by a novel mechanism complementing the current HAART therapy is becoming extremely important,” said CEO, Eugene Seymour.
“The HIV virus mutates constantly resulting in failure of HAART therapy regimens. In some countries, it has now mutated to such an extent that in up to 40% of patients the standard HAART therapy has become ineffective.”
The company’s nanoviricide class of drugs are being developed against a number of viral diseases, including H1N1 swine flu, H5N1 bird flu, seasonal Influenza, oral and genital Herpes, viral Hepatitis C, and Ebola virus, among others.
A recent study of anti-flu treatment FluCide showed that the drug was better than oseltamivir, or Tamiflu, with a 1,000-fold greater viral load reduction than the standard flu therapy, after optimization.
“The results of the current study have provided important insight to guide the next cycle of chemical optimization. We clearly know now that we are on the right path,” said president Anil R. Diwan.
Copyright © 2011 Proactive Investors USA & Canada
by Deborah Sterescu
NanoViricides (OTCBB:NNVC) reported Monday that its lead anti-HIV candidate achieved an efficacy level equivalent to a highly active anti-retroviral triple (HAART) drug cocktail in a recent animal study.
Treatment with the drug reduced HIV levels and protected human immune T-cells to the same extent as treatment with the cocktail did in a study of mice, said the company. The three drug-combination used for comparison is one of the current therapies recommended for patients with HIV.
NanoViricides, which uses special purpose nanomaterials to design viral therapies, also said that no evidence of drug toxicity was observed during the study, and that the investigational drug will now undergo further optimization.
The latest study verifies the company’s previous results, which found that nanoviricides had a significant therapeutic effect, equal or superior to the same three-drug cocktail in a mouse study.
The company’s nanoviricide therapy works to mimick cellular structures to which the virus binds, specifically attacking and dismantling them. By working differently than many combination therapies, the drug developer believes that the nanoviral treatment, or HIVCide, could compliment current standard-of-care, possibly achieving a “functional cure” of HIV/AIDS, NanoViricides said.
Although a functional cure is not a complete cure, it would allow an infected person to continue normal life even after discontinuation of therapy, maintaining undetectable viral load until a recurrence.
“Creating an adjunct drug that acts by a novel mechanism complementing the current HAART therapy is becoming extremely important,” said CEO, Eugene Seymour.
“The HIV virus mutates constantly resulting in failure of HAART therapy regimens. In some countries, it has now mutated to such an extent that in up to 40% of patients the standard HAART therapy has become ineffective.”
The company’s nanoviricide class of drugs are being developed against a number of viral diseases, including H1N1 swine flu, H5N1 bird flu, seasonal Influenza, oral and genital Herpes, viral Hepatitis C, and Ebola virus, among others.
A recent study of anti-flu treatment FluCide showed that the drug was better than oseltamivir, or Tamiflu, with a 1,000-fold greater viral load reduction than the standard flu therapy, after optimization.
“The results of the current study have provided important insight to guide the next cycle of chemical optimization. We clearly know now that we are on the right path,” said president Anil R. Diwan.
Copyright © 2011 Proactive Investors USA & Canada
Friday, July 15, 2011
Got HPV and HIV? Don't panic
Human papillomavirus (HPV) is currently the most common sexually transmitted infection (STI), perhaps because it is so easy to spread through skin-on-skin contact. For this reason, condoms can decrease, but not preclude, transmission of the virus during sex.
Various strains of the virus may cause genital warts on your penis or your ass. Generally painless, they can be occasionally itchy. They are almost always benign, the obvious exception being the strains that cause anal cancer.
The chemical you used to burn off the warts was probably liquid nitrogen. Even with this treatment, warts can reoccur. Depending on your age, you may choose to be vaccinated with Gardasil, but it works best if received prior to exposure to the virus.
Health Canada has approved the vaccine for young men from nine to 26, but oddly, they must pay for this particular preventive medicine, at a cost of up to $300, and it is not always easy to find a dispensing source. Hopefully, one day both boys and girls will be vaccinated for HPV just as they receive polio and measles vaccines, but we are far from that state now.
Though it is true that your risk of developing anal cancer increases if you have HPV and HIV, that risk is actually fairly minimal. That said, you are wise to remain vigilant regarding your anal health. If you notice changes to your ass in the form of bleeding, significant growth of the warts or other lesions in the first inch inside your anal opening — or anything else unusual — get to your doctor. If you can access the Lower Mainland, you can go to the infectious disease clinic at St Paul’s Hospital to get an anal PAP test.
Is there a need to alter your sexual behaviour now that your serological status has changed? Not necessarily. Because condoms cover only your penis, and because HPV rarely limits itself only to this area, they are not entirely protective. However, you want to minimize transmission as much as possible, so if you are with new or multiple partners, glove up.
Because of the incomplete protection condoms afford, you will need to advise new sexual partners of your potentially infectious status even if you engage in protected sex. You may wish to forgo anal sex with casual partners when your CD4 count is less than optimal. You will learn to read your body’s cues and can act accordingly.
If you are in a sexually exclusive relationship, you probably share strains of viruses, so you can relax regarding barrier protection, but, of course, use your best judgment and continue to talk openly about your health. The strains of HPV you have may not be oncogenic (cancer-producing), and you want to keep it that way. Your goal is to prevent transmission and reception of new strains while still enjoying great sex.
If your health is good, your CD4 count is robust and you are doing well on HAART (highly active anti-retroviral therapy), your chances of developing anal cancer are reduced. As horrible as it sounds, anal cancer is less deadly and metastatic (easily spreading) than its sister cervical cancer, which women have learned to manage through routine PAP tests for years now. You guys must now be vocal and persistent in demanding the same good medical care.
HPV is primarily a cosmetic problem, providing you monitor your body for changes. Since it has become ubiquitous in the community, you needn’t fear rejection or embarrassment because of it.
So all in all, though having HIV and HPV is not good news, it is not terrible news, either. Several decades ago, these diagnoses would have threatened far more serious consequences. Now they signal a need for continued vigilance and monitoring of your health status — not such a bad thing, really.
The point is that this is not a death sentence. It is not even news about which you need to panic. You have illnesses that compromise your immune system, and luckily, medicine is catching up with necessary treatments, although, alas, cures are still unavailable.
Political pressure is needed to make Gardasil available for young men. Those in non-urban areas often still lack access to anal PAP tests and dignified treatment. We do not yet live in the world we hope for or deserve.
Still, you can have a long and satisfying life. I encourage you to do so. This is a situation where you can happily celebrate your half-full glass.
Got a question for Dr Ren? asktheexpert@xtra.ca
Copyright 2011 Xtra! Canada's Gay & Lesbian News
Human papillomavirus (HPV) is currently the most common sexually transmitted infection (STI), perhaps because it is so easy to spread through skin-on-skin contact. For this reason, condoms can decrease, but not preclude, transmission of the virus during sex.
Various strains of the virus may cause genital warts on your penis or your ass. Generally painless, they can be occasionally itchy. They are almost always benign, the obvious exception being the strains that cause anal cancer.
The chemical you used to burn off the warts was probably liquid nitrogen. Even with this treatment, warts can reoccur. Depending on your age, you may choose to be vaccinated with Gardasil, but it works best if received prior to exposure to the virus.
Health Canada has approved the vaccine for young men from nine to 26, but oddly, they must pay for this particular preventive medicine, at a cost of up to $300, and it is not always easy to find a dispensing source. Hopefully, one day both boys and girls will be vaccinated for HPV just as they receive polio and measles vaccines, but we are far from that state now.
Though it is true that your risk of developing anal cancer increases if you have HPV and HIV, that risk is actually fairly minimal. That said, you are wise to remain vigilant regarding your anal health. If you notice changes to your ass in the form of bleeding, significant growth of the warts or other lesions in the first inch inside your anal opening — or anything else unusual — get to your doctor. If you can access the Lower Mainland, you can go to the infectious disease clinic at St Paul’s Hospital to get an anal PAP test.
Is there a need to alter your sexual behaviour now that your serological status has changed? Not necessarily. Because condoms cover only your penis, and because HPV rarely limits itself only to this area, they are not entirely protective. However, you want to minimize transmission as much as possible, so if you are with new or multiple partners, glove up.
Because of the incomplete protection condoms afford, you will need to advise new sexual partners of your potentially infectious status even if you engage in protected sex. You may wish to forgo anal sex with casual partners when your CD4 count is less than optimal. You will learn to read your body’s cues and can act accordingly.
If you are in a sexually exclusive relationship, you probably share strains of viruses, so you can relax regarding barrier protection, but, of course, use your best judgment and continue to talk openly about your health. The strains of HPV you have may not be oncogenic (cancer-producing), and you want to keep it that way. Your goal is to prevent transmission and reception of new strains while still enjoying great sex.
If your health is good, your CD4 count is robust and you are doing well on HAART (highly active anti-retroviral therapy), your chances of developing anal cancer are reduced. As horrible as it sounds, anal cancer is less deadly and metastatic (easily spreading) than its sister cervical cancer, which women have learned to manage through routine PAP tests for years now. You guys must now be vocal and persistent in demanding the same good medical care.
HPV is primarily a cosmetic problem, providing you monitor your body for changes. Since it has become ubiquitous in the community, you needn’t fear rejection or embarrassment because of it.
So all in all, though having HIV and HPV is not good news, it is not terrible news, either. Several decades ago, these diagnoses would have threatened far more serious consequences. Now they signal a need for continued vigilance and monitoring of your health status — not such a bad thing, really.
The point is that this is not a death sentence. It is not even news about which you need to panic. You have illnesses that compromise your immune system, and luckily, medicine is catching up with necessary treatments, although, alas, cures are still unavailable.
Political pressure is needed to make Gardasil available for young men. Those in non-urban areas often still lack access to anal PAP tests and dignified treatment. We do not yet live in the world we hope for or deserve.
Still, you can have a long and satisfying life. I encourage you to do so. This is a situation where you can happily celebrate your half-full glass.
Got a question for Dr Ren? asktheexpert@xtra.ca
Copyright 2011 Xtra! Canada's Gay & Lesbian News
Ultrasound May Determine Heart Attack Risk in HIV Patients
Risk 10 times higher in HIV patients with abnormal results compared with general population: study
People with HIV are at increased risk for blood vessel blockages, and new research shows heart ultrasounds can help determine if these patients are more likely to suffer a serious or fatal heart attack.
A report from the American Heart Association revealed that the risk for heart attack among people with HIV who have abnormal heart ultrasound tests or "stress echoes" is 10 times greater than in the general population and more than three times higher than in people without HIV who have abnormal heart ultrasounds.
"We looked at whether stress echo can help predict risk in a high-risk group — HIV patients with known or suspected heart disease — and determine whether they have a high or low risk of heart attack and death in the future," the study's senior author, Dr. Farooq A. Chaudhry, associate professor of medicine at Columbia University College of Physicians and Surgeons and associate chief of cardiology and director of echocardiography at St. Luke's Roosevelt Hospital Center in New York City, said in an American Heart Association news release.
In conducting stress echoes on 311 HIV patients averaging 52 years of age with known or suspected heart disease, researchers found that 26 percent had abnormal ultrasounds. Within an average of about three years, there were 14 cardiac deaths and 17 nonfatal heart attacks.
The study authors concluded that the HIV patients who had normal stress echo tests had on average a less than 1 percent per year risk for serious or fatal heart attack -- the same risk as in the general healthy population. In sharp contrast, the risk of heart attack among the HIV patients with abnormal stress echo test results was almost 12 percent per year.
The study, published in the current issue of Circulation: Cardiovascular Imaging, found that 100 percent of HIV patients with normal heart ultrasounds survived in the year following the test and 98 percent were alive at four years. Those survival rates dropped to 92 percent at one year and 62 percent at four years for people with HIV that had abnormal stress echoes, the report indicated.
"Although we did not study which treatments are most effective for these patients, HIV patients who have abnormal stress echocardiography should probably be monitored and treated more aggressively to prevent heart attack and death," said Chaudhry. "Conversely, patients with a normal stress echo might not need such aggressive interventions."
The American Heart Association provides more information on HIV and the heart.
Copyright © 2011 HealthDay. All rights reserved
Risk 10 times higher in HIV patients with abnormal results compared with general population: study
People with HIV are at increased risk for blood vessel blockages, and new research shows heart ultrasounds can help determine if these patients are more likely to suffer a serious or fatal heart attack.
A report from the American Heart Association revealed that the risk for heart attack among people with HIV who have abnormal heart ultrasound tests or "stress echoes" is 10 times greater than in the general population and more than three times higher than in people without HIV who have abnormal heart ultrasounds.
"We looked at whether stress echo can help predict risk in a high-risk group — HIV patients with known or suspected heart disease — and determine whether they have a high or low risk of heart attack and death in the future," the study's senior author, Dr. Farooq A. Chaudhry, associate professor of medicine at Columbia University College of Physicians and Surgeons and associate chief of cardiology and director of echocardiography at St. Luke's Roosevelt Hospital Center in New York City, said in an American Heart Association news release.
In conducting stress echoes on 311 HIV patients averaging 52 years of age with known or suspected heart disease, researchers found that 26 percent had abnormal ultrasounds. Within an average of about three years, there were 14 cardiac deaths and 17 nonfatal heart attacks.
The study authors concluded that the HIV patients who had normal stress echo tests had on average a less than 1 percent per year risk for serious or fatal heart attack -- the same risk as in the general healthy population. In sharp contrast, the risk of heart attack among the HIV patients with abnormal stress echo test results was almost 12 percent per year.
The study, published in the current issue of Circulation: Cardiovascular Imaging, found that 100 percent of HIV patients with normal heart ultrasounds survived in the year following the test and 98 percent were alive at four years. Those survival rates dropped to 92 percent at one year and 62 percent at four years for people with HIV that had abnormal stress echoes, the report indicated.
"Although we did not study which treatments are most effective for these patients, HIV patients who have abnormal stress echocardiography should probably be monitored and treated more aggressively to prevent heart attack and death," said Chaudhry. "Conversely, patients with a normal stress echo might not need such aggressive interventions."
The American Heart Association provides more information on HIV and the heart.
Copyright © 2011 HealthDay. All rights reserved
Pills found to be highly effective in preventing HIV transmission
By Thomas H. Maugh II, Los Angeles Times
Experts hail a pair of trials involving heterosexual couples in Africa as a breakthrough in AIDS prevention. The studies show that taking a pill containing one or two drugs each day can decrease transmission of HIV by as much as three-quarters.
Taking a daily pill containing either one or two anti-HIV drugs can reduce transmission of the virus by as much as three-quarters among heterosexual couples, two studies in Africa have shown — a breakthrough finding that promises to intensify a new focus on AIDS prevention.
The results were so compelling that the larger study was halted early and the drugs given to all the participants, researchers said Wednesday.
In the absence of a vaccine to protect against the virus, this new approach, termed pre-exposure prophylaxis, may be the best hope for slowing or even halting the spread of the deadly plague throughout the developing world. U.S. health officials are beginning to prepare guidelines for how the drugs could be used in this country to prevent new infections.
The findings "are two more nails in the coffin of HIV," said Mitchell Warren, executive director of the New York-based AIDS Vaccine Advocacy Coalition. "We are seeing similar results in different populations, and that gives us more certainty that these results are real."
A study of gay men reported in November showed that one of the drugs in the new trial could reduce the spread of HIV by as much as 70% when taken regularly by uninfected individuals. But a study released this year found that the drugs did not show a similar benefit among uninfected heterosexual women.
The strength of the new findings suggests that the study involving women may have been flawed.
"Our results provide clear evidence that this works in heterosexuals," said Dr. Jared Baeten of the University of Washington, co-chair of the new study.
The last year has brought several breakthroughs in AIDS prevention research, said Kevin Frost, chief executive of amfAR, the Foundation for AIDS Research. In addition to this latest finding and the study involving gay men, a study released last July found that microbicides could sharply reduce HIV transmission in women and a study in HIV-positive people showed that treating the infected person intensively could reduce transmission by as much as 96%.
Given those and other developments, "we find ourselves in a place where we have an extraordinary opportunity to radically alter the trajectory of the epidemic," Frost said. "The science is in place. We could do it with the tools we have available. It's no longer a question of, can we do this? The question is, will we do it?"
The new results are scheduled to be presented next week at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Rome, but were released early.
One trial enrolled 4,758 couples in Kenya and Uganda in which one partner was HIV-positive and the other was not. A third of the uninfected participants received a daily pill containing tenofovir, a third received a daily pill containing tenofovir in combination with emtricitabine, and a third received a placebo.
Tenofovir is marketed as Viread and the two-drug combination as Truvada by Gilead Sciences Inc. of Foster City, Calif. They are available generically in many countries for as little as 25 cents per pill, according to the World Health Organization
All couples also received condoms and counseling about how to prevent infection.
By the end of May, researchers had identified 18 new infections among the group receiving Viread, 13 among those receiving Truvada and 47 among those receiving the placebo. That corresponds to a 62% reduction in transmission among those receiving Viread and a 73% reduction among those receiving Truvada.
The second trial, sponsored by the U.S. Centers for Disease Control and Prevention, studied 1,200 healthy, sexually active males and females in Botswana. About half received Truvada and half a placebo. Among the 601 participants who took Truvada, there were nine new infections, compared with 24 among the 599 who received placebo. That amounts to a 62.6% reduction in new infections.
Among those participants who took the drugs regularly, researchers observed an even greater reduction — 77.9% — in new infections.
No significant side effects were observed in either trial. "The perception is that these drugs are really toxic," said Dr. Thomas J. Coates, an infectious diseases specialist at UCLA's Geffen School of Medicine. "They are not. The current generation is really quite safe."
Dr. Jonathan Mermin, director of the CDC's Division of HIV/AIDS Prevention, said the agency would immediately begin working with other public health groups to establish guidelines for using the drugs prophylactically in this country. Physicians should await those guidelines before prescribing the drugs, he said, but if they believe it is imperative to do it, they should adhere to the guidelines previously announced for using them in gay men.
Dr. Robert M. Grant of UC San Francisco's Gladstone Institute of Virology and Immunology speculated that the drugs might work even better in the United States than they did in Africa. People in this country "are more accustomed to using pills for prevention," he noted, and thus more likely to take the drugs regularly.
Copyright © 2011, Los Angeles Times
By Thomas H. Maugh II, Los Angeles Times
Experts hail a pair of trials involving heterosexual couples in Africa as a breakthrough in AIDS prevention. The studies show that taking a pill containing one or two drugs each day can decrease transmission of HIV by as much as three-quarters.
Taking a daily pill containing either one or two anti-HIV drugs can reduce transmission of the virus by as much as three-quarters among heterosexual couples, two studies in Africa have shown — a breakthrough finding that promises to intensify a new focus on AIDS prevention.
The results were so compelling that the larger study was halted early and the drugs given to all the participants, researchers said Wednesday.
In the absence of a vaccine to protect against the virus, this new approach, termed pre-exposure prophylaxis, may be the best hope for slowing or even halting the spread of the deadly plague throughout the developing world. U.S. health officials are beginning to prepare guidelines for how the drugs could be used in this country to prevent new infections.
The findings "are two more nails in the coffin of HIV," said Mitchell Warren, executive director of the New York-based AIDS Vaccine Advocacy Coalition. "We are seeing similar results in different populations, and that gives us more certainty that these results are real."
A study of gay men reported in November showed that one of the drugs in the new trial could reduce the spread of HIV by as much as 70% when taken regularly by uninfected individuals. But a study released this year found that the drugs did not show a similar benefit among uninfected heterosexual women.
The strength of the new findings suggests that the study involving women may have been flawed.
"Our results provide clear evidence that this works in heterosexuals," said Dr. Jared Baeten of the University of Washington, co-chair of the new study.
The last year has brought several breakthroughs in AIDS prevention research, said Kevin Frost, chief executive of amfAR, the Foundation for AIDS Research. In addition to this latest finding and the study involving gay men, a study released last July found that microbicides could sharply reduce HIV transmission in women and a study in HIV-positive people showed that treating the infected person intensively could reduce transmission by as much as 96%.
Given those and other developments, "we find ourselves in a place where we have an extraordinary opportunity to radically alter the trajectory of the epidemic," Frost said. "The science is in place. We could do it with the tools we have available. It's no longer a question of, can we do this? The question is, will we do it?"
The new results are scheduled to be presented next week at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Rome, but were released early.
One trial enrolled 4,758 couples in Kenya and Uganda in which one partner was HIV-positive and the other was not. A third of the uninfected participants received a daily pill containing tenofovir, a third received a daily pill containing tenofovir in combination with emtricitabine, and a third received a placebo.
Tenofovir is marketed as Viread and the two-drug combination as Truvada by Gilead Sciences Inc. of Foster City, Calif. They are available generically in many countries for as little as 25 cents per pill, according to the World Health Organization
All couples also received condoms and counseling about how to prevent infection.
By the end of May, researchers had identified 18 new infections among the group receiving Viread, 13 among those receiving Truvada and 47 among those receiving the placebo. That corresponds to a 62% reduction in transmission among those receiving Viread and a 73% reduction among those receiving Truvada.
The second trial, sponsored by the U.S. Centers for Disease Control and Prevention, studied 1,200 healthy, sexually active males and females in Botswana. About half received Truvada and half a placebo. Among the 601 participants who took Truvada, there were nine new infections, compared with 24 among the 599 who received placebo. That amounts to a 62.6% reduction in new infections.
Among those participants who took the drugs regularly, researchers observed an even greater reduction — 77.9% — in new infections.
No significant side effects were observed in either trial. "The perception is that these drugs are really toxic," said Dr. Thomas J. Coates, an infectious diseases specialist at UCLA's Geffen School of Medicine. "They are not. The current generation is really quite safe."
Dr. Jonathan Mermin, director of the CDC's Division of HIV/AIDS Prevention, said the agency would immediately begin working with other public health groups to establish guidelines for using the drugs prophylactically in this country. Physicians should await those guidelines before prescribing the drugs, he said, but if they believe it is imperative to do it, they should adhere to the guidelines previously announced for using them in gay men.
Dr. Robert M. Grant of UC San Francisco's Gladstone Institute of Virology and Immunology speculated that the drugs might work even better in the United States than they did in Africa. People in this country "are more accustomed to using pills for prevention," he noted, and thus more likely to take the drugs regularly.
Copyright © 2011, Los Angeles Times
Thursday, July 14, 2011
Stop the ADAP Crisis!
By Sonia Rastogi
The AIDS Drug Assistance Program (ADAP), is a safety net that provides life-saving medications to people living with HIV. Due to a funding crisis, as of September 2010, 3,441 people are on waiting lists to access medication. South Carolinians, Pat Kelly, founder of A Family Affair and founding member of the PWN, and Bonetta Graves, coordinator at Wateree AIDS Task Force, discuss the need for action in their state where the ADAP waiting list is growing.
Pat and Bonetta spoke with SC Sen. Graham about the state’s growing waiting list at the ADAP Summit in D.C. but South Carolina will not invest more money. “If one-third of the HIV-positive people in South Carolina come out to rally … then the state would not be able to cut ADAP funding,” but right now legislators do not see the need, Pat said.
It is vital to think about how the ADAP crisis affects the lives of HIV-positive people’s family members and children. Bonetta emphasized that for women, “there are a lot of things [they] are going to be cut off from,” without HIV treatment, including the ability to work and take care of their family.
TAKE ACTION! Step one: EDUCATION. Find out how you or your community is affected by the ADAP crisis: does ADAP provide your life-saving medication? “Somebody is going to have to pull their heads up out of the sand… to get started,” says Bonetta. Step two: EMPOWERMENT. “We need to start looking at medication from a human rights standpoint.” Pat says “We have a right to medication. … It is a right to health!” Step three: SPEAK OUT! Contact your local ASO or e-mail the PWN at pwn@womenhiv.org.
Sonia Rastogi is the PWN’s Communications Coordinator based in Oakland, CA. Pat Kelly, based in Orangeburg, South Carolina, is the founder of A Family Affair and founding member of PWN.
This article is from PWN’s Fall 2010 Newsletter.
By Sonia Rastogi
The AIDS Drug Assistance Program (ADAP), is a safety net that provides life-saving medications to people living with HIV. Due to a funding crisis, as of September 2010, 3,441 people are on waiting lists to access medication. South Carolinians, Pat Kelly, founder of A Family Affair and founding member of the PWN, and Bonetta Graves, coordinator at Wateree AIDS Task Force, discuss the need for action in their state where the ADAP waiting list is growing.
Pat and Bonetta spoke with SC Sen. Graham about the state’s growing waiting list at the ADAP Summit in D.C. but South Carolina will not invest more money. “If one-third of the HIV-positive people in South Carolina come out to rally … then the state would not be able to cut ADAP funding,” but right now legislators do not see the need, Pat said.
It is vital to think about how the ADAP crisis affects the lives of HIV-positive people’s family members and children. Bonetta emphasized that for women, “there are a lot of things [they] are going to be cut off from,” without HIV treatment, including the ability to work and take care of their family.
TAKE ACTION! Step one: EDUCATION. Find out how you or your community is affected by the ADAP crisis: does ADAP provide your life-saving medication? “Somebody is going to have to pull their heads up out of the sand… to get started,” says Bonetta. Step two: EMPOWERMENT. “We need to start looking at medication from a human rights standpoint.” Pat says “We have a right to medication. … It is a right to health!” Step three: SPEAK OUT! Contact your local ASO or e-mail the PWN at pwn@womenhiv.org.
Sonia Rastogi is the PWN’s Communications Coordinator based in Oakland, CA. Pat Kelly, based in Orangeburg, South Carolina, is the founder of A Family Affair and founding member of PWN.
This article is from PWN’s Fall 2010 Newsletter.
Wednesday, July 13, 2011
Double Immunity
Dr. Stephen O’Brien’s work with HIV led to a discovery that could one day help scientists treat or prevent HIV infection: People from some European populations carry a genetic mutation that prevents HIV from entering their white blood cells. O’Brien hypothesizes that this mutation, dating back 700 years, may have been a selective advantage during the bubonic plague, as it is today, with the onslaught of HIV. From Evolution: “Evolutionary Arms Race.”
The genetic scripts written in DNA code constantly undergo changes, or mutations. At times, these mistakes in a gene’s message can be harmful; often, they have no significant effect. Occasionally, though, a mutation confers a survival advantage in the face of an environmental change. Most of the non-carriers of the mutation die, and those with the mutation are able to reproduce. With that powerful evolutionary selection force, the gene can become common in a population.
Recently, scientists were astonished to find that some individuals did not become infected with HIV, even after repeated exposure to the deadly virus.
For some reason, they were immune. A long and difficult scientific search, using blood samples from hundreds of HIV-resistant patients, finally teased out the genetic explanation. Resistant individuals had in their cells two copies of a mutation that disrupted the entryway through which HIV viruses entered white blood cells. People who inherited just one copy of the change could become infected, but their disease progressed more slowly.
With this being such a recent epidemic, where did peoples’ immunity come from?
Another puzzle was the way this resistance is distributed throughout the world. In some Northern European populations it is relatively common. In Southern Europeans it is more rare, and it is almost entirely absent in Africans, Asians, and Native Americans. Logically, the mutation must have occurred in the past, acting as a defense against a different, previous epidemic caused — like the AIDS epidemic — by a pathogen that also targeted white blood cells.
Reading a chronological history, biologists traced the HIV-resistance gene mutation back about 700 years. That was the time at which the Black Death — bubonic plague — swept like a deadly scythe through Europe, killing one-third of the population. Then, as now, there were individuals who survived the lethal organism, perhaps because it could not enter their white blood cells. The areas that were hardest hit by the Black Plague match those where the gene for HIV resistance is the most common today.
At present, scientists are trying to infect such resistant cells with bubonic plague bacteria to test the hypothesis that the mutation in the CCR-5 receptor gene could have thwarted the plague in the Middle Ages, as it does HIV today. If it turns out that this mutation does protect against the plague, this coincidence will be yet another illustration of what scientists are finding over and over in the human genome: Nature’s past successes often remain part of our genetic toolbox.
Copyright © 2001 WGBH Educational Foundation and Clear Blue Sky Productions, Inc. All rights reserved.
Evolutionary Arms Race [VHS]
Dr. Stephen O’Brien’s work with HIV led to a discovery that could one day help scientists treat or prevent HIV infection: People from some European populations carry a genetic mutation that prevents HIV from entering their white blood cells. O’Brien hypothesizes that this mutation, dating back 700 years, may have been a selective advantage during the bubonic plague, as it is today, with the onslaught of HIV. From Evolution: “Evolutionary Arms Race.”
The genetic scripts written in DNA code constantly undergo changes, or mutations. At times, these mistakes in a gene’s message can be harmful; often, they have no significant effect. Occasionally, though, a mutation confers a survival advantage in the face of an environmental change. Most of the non-carriers of the mutation die, and those with the mutation are able to reproduce. With that powerful evolutionary selection force, the gene can become common in a population.
Recently, scientists were astonished to find that some individuals did not become infected with HIV, even after repeated exposure to the deadly virus.
For some reason, they were immune. A long and difficult scientific search, using blood samples from hundreds of HIV-resistant patients, finally teased out the genetic explanation. Resistant individuals had in their cells two copies of a mutation that disrupted the entryway through which HIV viruses entered white blood cells. People who inherited just one copy of the change could become infected, but their disease progressed more slowly.
With this being such a recent epidemic, where did peoples’ immunity come from?
Another puzzle was the way this resistance is distributed throughout the world. In some Northern European populations it is relatively common. In Southern Europeans it is more rare, and it is almost entirely absent in Africans, Asians, and Native Americans. Logically, the mutation must have occurred in the past, acting as a defense against a different, previous epidemic caused — like the AIDS epidemic — by a pathogen that also targeted white blood cells.
Reading a chronological history, biologists traced the HIV-resistance gene mutation back about 700 years. That was the time at which the Black Death — bubonic plague — swept like a deadly scythe through Europe, killing one-third of the population. Then, as now, there were individuals who survived the lethal organism, perhaps because it could not enter their white blood cells. The areas that were hardest hit by the Black Plague match those where the gene for HIV resistance is the most common today.
At present, scientists are trying to infect such resistant cells with bubonic plague bacteria to test the hypothesis that the mutation in the CCR-5 receptor gene could have thwarted the plague in the Middle Ages, as it does HIV today. If it turns out that this mutation does protect against the plague, this coincidence will be yet another illustration of what scientists are finding over and over in the human genome: Nature’s past successes often remain part of our genetic toolbox.
Copyright © 2001 WGBH Educational Foundation and Clear Blue Sky Productions, Inc. All rights reserved.
Evolutionary Arms Race [VHS]
Monday, July 11, 2011
The Anal Dialogues
by Trenton Straube
Rectal microbicides-topical gels, ointments and lubricants laced with ?drugs to block HIV-could help stop the spread of the virus. So why is it taking so long to develop them? For one thing, an unwillingness to talk about sex-especially anal sex. Given the potential of microbicides' protective power, it's time we loosen our tongues in order to start saving lives.
In 1992, at a meeting of the Delaware Valley Women and AIDS Network, Anna Forbes first heard about experimental compounds called vaginal microbicides. It sparked an “A-ha!” moment for the longtime advocate for women’s health. Forbes saw right away how a microbicide—a gel, cream, lubricant or other topical agent that could be applied to the vagina to inhibit sexual transmission of HIV—would offer a much-needed method of protection to women, especially those who couldn’t get their partners to use condoms. And as an advocate for gay men’s health, Forbes also imagined how a rectal microbicide could offer a valuable prevention tool for anal sex for both men and women.
Women and gay men share the common concern of having their health needs respected and addressed, Forbes says. “A receptive partner is a receptive partner.” Effective microbicides would arm both male and female receptive partners with prevention tools that could save their lives.
But when she started talking about the notion of vaginal and rectal microbicides, Forbes found that even people on the cutting edge of women’s and gay men’s health advocacy were uncomfortable talking so specifically about sex, especially anal sex. It showed, according to Forbes, “this weird way that homophobia and sexism intersected.” And it pointed out “the well-kept secret that women have anal sex too.”
Undaunted by the reluctance of many of her peers, and inspired by the potential lifesaving power of microbicides, Forbes set out to convince the world to think similarly, working for a decade at the Global Campaign for Microbicides (she recently moved into consulting). The topic continued to be a hard sell. “The trouble with microbicides in comparison to pills and injections,” Forbes says, “is that they are applied ‘down there.’ You can’t talk about microbicides without talking about sex.”
Thanks in part to the unflagging efforts of Forbes and other visionary leaders (along with increasingly promising research data), the scientific and advocacy communities began rallying around vaginal microbicide research. Yet, very few people supported the notion of a rectal version. Forbes recalls the first time she saw the topic discussed in the print media, in a 1999 POZ article, “Beyond Condoms: Life After Latex,” in which journalist Michael Scarce presciently wrote: “The astonishing thing is, gay men raise no voice to advocate for a form of HIV prevention that maximizes pleasure and safety.” In Colorado the next year, at the second LGBTI Health Summit (the initials embrace lesbian, gay, bisexual, trans and intersex people), Forbes gave a presentation on the need for rectal microbicides. Only about five people showed up. Clearly, interest in the subject was lacking—even among the most likely benefactors, gay men.
Then, another A-ha! moment: The messenger, Forbes realized, needed to double as the message. A straight woman couldn’t draw the same attention in the gay community as a gay man could. “We needed a gay male face, somebody with a track record in the [prevention] field,” she says. She envisioned an organized group led by a gay man working to promote rectal microbicides and in the process tackling the taboos associated with anal sex. In 2005, Forbes approached some likely advocates: Marc-André LeBlanc from the Canadian AIDS Society, Julie Davids from CHAMP (Community HIV/AIDS Mobilization Project) and Jim Pickett of the AIDS Foundation of Chicago. Although all were overextended, they agreed on the need to fight for a new form of prevention. Thus, the International Rectal Microbicide Advocates (IRMA) group was formed.
IRMA began modestly. “We had a listserv, and our goal was to get people to share information [about rectal microbicides],” says Pickett, IRMA’s chair (its out, gay face). He recalls begging people at the 2005 National HIV Prevention Conference to join the email group. Many resisted, arguing that rectal microbicides were too futuristic and that advocating for them would deflect resources from the priority concern at the moment: condoms. “People would almost groan when Jim would get on stage,” says Ian McGowan, MD, a leading microbicide researcher.
People’s reluctance to talk about butts (male and female), similarly muzzled scientists. As recently as a few years ago, many researchers scoffed at the very idea of a rectal microbicide, claiming human anatomy made it impossible. Unlike the vagina, which is essentially an enclosed container, the five-foot-long colon, Pickett says, is “like the Holland Tunnel.” There was the question of how far ejaculate could travel up the colon. Would the colon’s entire surface have to be protected? How much gel would be required—and how much could a body take? Scientists didn’t know. That is, until Craig Hendrix, MD, at Johns Hopkins University, conducted experiments involving some brave volunteers, faux microbicides and a hollow dildo that squirted an “ejaculate” traceable by MRI scans. (Read one volunteer’s hilarious account, “Putting My Ass on the Line,” on the IRMA blog at irma-rectalmicrobicides.blogspot.com.)The experiments proved that the faux microbicide traveled well with the ejaculate and that to be effective, a microbicide would likely need to coat only the lowest 4 to 6 inches of the rectum and anal canal. Furthermore, researchers determined that ?humans could tolerate up to 30 milliliters (ml) of gel administered anally. However, the gel currently being studied requires only 4 ml, less than a teaspoon.
If these details make you squirm, you wouldn’t want Pickett’s job. The gregarious advocate constantly finds himself discussing anal sex and all its details—often in front of crowds. He does so as easily as most guys rattle off sports stats, employing honesty and humor that prove disarming. Equally important, he and IRMA back up their cause with something scientists recognize: cold, hard data.
Perhaps IRMA’s most visible work is three game-changing reports it published in conjunction with the biennial International Microbicides Conference. The first, Rectal Microbicides: Investments & Advocacy in 2006, compiled what research was being done and where—a tricky task. “A lot of researchers were concerned that if ‘anal’ or ‘rectal’ appeared in research proposals or reports, they wouldn’t get funded, so they’d scrub their papers so those words wouldn’t show up,” LeBlanc says. “Instead, they would refer to ‘topical use of products’ or other language.” And because of the dangers surrounding the subject—male-to-male sex is illegal in many countries, including 31 in sub-Saharan Africa—IRMA first had to gain researchers’ trust, proving they were not raging advocates who would alienate and antagonize. Their professionalism paid off, and the report was a hit. “It showed we were serious,” Pickett says, “and we got hundreds of new members.”
The next two reports, Less Silence, More Science in 2008 and From Promise to Product: Advancing Rectal Microbicide Research and Advocacy in 2010 (all the reports are available at rectalmicrobicides.org), addressed the reality that anal sex is more common than believed. The reports showed that among women anal sex remains an overlooked driver of the AIDS epidemic. (Because there are more women in the world than gay men, the overall number of women having receptive anal sex is higher than that of gay men.) By amassing data and research from across the globe, the reports argue effectively for developing rectal microbicides. A sampling from the 2010 report:
Beyond advocacy and education about anal sex, IRMA helps shape a unified research agenda, coordinating studies among disparate, often unconnected researchers across the globe. (“We herd the cats,” Pickett says.) It directs funds to needed areas (though it doesn’t directly fund research). It digests complex research into talking points for mainstream media, translates reports into other languages, asks important questions and pursues answers.
Along the way, microbicide research has produced some immediate benefits. At a 2006 Cape Town AIDS conference, biomedical scientists with the Population Council presented data on the possible link between anal lubes and HIV risk. (The same team, lead by David Phillips, PhD, reported in 2000 that the spermicide nonoxynol-9 damaged linings of the rectum and vagina, thus increasing the risk for HIV and herpes—findings that resulted in N-9 being removed from most condoms.) The lube presentation, Pickett says, sparked his own revelatory moment. “We were like, The lubes we have are not tested for safety? We have to get research on this. Yes, we want rectal microbicides, but people are using lubes today!”
At the time, little was known about the popularity, use and safety of anal lubes—in the United States, lubes must be tested for vaginal irritation (in rabbits) but not for rectal use. To build a research database, IRMA conducted a survey. “We thought we’d get a few dozen answers,” LeBlanc says, “but we had nearly 9,000 people respond from nearly 100 countries.” The survey was translated into six languages. “As far as we know, it’s the largest survey on anal sex in the world.” (IRMA is following up with a survey on douches and enemas, which might affect HIV/STI risk and offer a mode of microbicide delivery.)
The survey results have been pivotal to researchers such as Charlene Dezzutti, PhD, a lab director at the Microbicide Trials Network, who is examining the lube qualities that might affect HIV risk and be of use in microbicides. (For more on lube safety and her findings, see "Slippery Slopes," on the following page.)
IRMA’s hard work is paying off elsewhere too. The energetic listserv now includes more than 1,000 members. Pickett manages its daily conversation from his office at the AIDS Foundation of Chicago (AFC), where he is director of advocacy (IRMA is a project of AFC). “I think the overarching thing that has made us successful is that we bring together scientists and advocates,” Pickett says. “There is no other forum like this. An advocate in Thailand can post an opinion, and a researcher in Peru or London or Pittsburgh can comment all in the same hour—people find it really useful.”
Discussions range across prevention topics including study results, female condoms and Uganda’s Anti-Homosexuality Bill. One round of emails discussed a British safe-sex musical video with the problematic lyrics, “Something to remember as a rule of thumb, one up the bum and there’s no harm done…one up the bum and you won’t be a mum.” (Listserv members contacted the video’s creators to argue against promoting anal intercourse as a risk-free way to avoid getting pregnant.)
“[IRMA is] doing all the right stuff,” says Forbes, speaking like a proud momma. “They’re recognizing the importance of geographic and constituency diversities, and they’re promoting everybody having the discussion in whatever way makes sense in their own communities and encouraging people to share ownership—exactly what we need.”
This year, IRMA had good news to trumpet. A Microbicide Trials Network study, MTN-006, found that people who used a rectal gel containing 1 percent tenofovir, an HIV drug, had high concentrations of the med in rectal tissue and lower concentrations in the blood stream, which could mean fewer side effects. The downside: A single dose before sex probably won’t be effective.
Today, people no longer groan when Pickett takes the stage. “People came up to me after the CAPRISA results [a large South African microbicide study] and said, ‘For all these years, I thought you were crazy, but you’ve proven me wrong. Now I understand why you had such a belief in this.’”
Perhaps IRMA’s biggest success is simply getting people to confront the realities of anal sex and HIV. Because without honest dialogue about sex—whether at an international science conference, a sex education class or an intimate chat between lovers—we are never going to stop this epidemic. And that’s something we all need to speak up for.
Slippery Slopes
Can lubes increase the risk of HIV during anal sex?
A slew of recent studies suggest that using lubes for unprotected anal sex may increase the risk of HIV, and that some lubes may harm the rectum’s thin protective layer of cells (the epithelium). It’s premature to know which brands to avoid, says Marc-André LeBlanc, a lube advocate with the International Rectal Microbicide Advocates (IRMA). Most research has been done in laboratories, and it isn’t certain whether the findings translate to humans—or whether the products’ lubricating benefits outweigh their potential harm. But one fact is certain: “The best way to prevent acquiring HIV and STIs [sexually transmitted infections] during anal sex is still using male or female condoms,” LeBlanc says. “And we know that using lubes with condoms decreases the risk of the condom slipping or breaking—a big bonus.”
In the meantime, here’s a highlight of what scientists are investigating and how lube qualities might affect the success of microbicides:
Starting to Gel
Microbicides: Where they are now and where they are going
VAGINAL GEL: After two decades of disappointing results, a breakthrough arrived last summer with results of the CAPRISA 004 trial: Women using a gel containing 1 percent tenofovir (an HIV med found in Atripla, Viread and Truvada) had 39 percent fewer infections than those using a placebo. Women with 80 percent adherence to the two necessary applications per sex act (12 hours before, then immediately after) had even fewer infections. The gel also offered protection against herpes.
What’s Next: Studies are under-way to confirm CAPRISA 004 results and determine the most effective concentrations and doses, but the global economic crisis has depleted funding, slowing progress. On the bright side, the drug from the vaginal gel is showing up in rectal tissue, so one product might offer women protection in both areas.
RECTAL GEL: Microbicide Trials Network study MTN-006 looked at using the vaginal tenofovir gel rectally, with promising results announced in February. Although the vaginal formulation harmed the rectal lining and caused gastrointestinal distress, Charlene Dezzutti’s team developed a better version with less glycerin. And, says Ian McGowan, PhD, a co-principal study investigator, “We found that when you give the drug topically, you get very high concentrations in the rectal tissue—a hundred times the amount from a single Viread tablet.” A few caveats: Tenofovir works not by directly attacking and disarming HIV, but by accumulating in the tissue and CD4 cells HIV will attack, preventing HIV from replicating once it invades the cell. Unfortunately, this accumulation demands repeated doses. “I think MTN-006 suggests,” McGowan says, “that if you just take one dose, orally or rectally, half an hour before exposure, I would doubt you’d be protected.”
What’s Next: A Phase I study (MTN-007) on the safety and acceptability of the rectal tenofovir gel; and Project Gel, investigating the use of rectal microbicides among African-American and Latino men who have sex with men (MSM). “It’s critical,” McGowan says, “because these are the people who are getting infected and need the product.”
FUTURE IDEAS AND EXPERIMENTS:
Other HIV meds or combos—or completely new compounds—may offer better protection than tenofovir as microbicides (hint: HIV drugs that are too toxic as pills may work as topical solutions).
Different modes of delivery: How about a slowly dissolving ring instead of a vaginal gel? Or combining a microbicide with a vaccine, to help prepare the immune system for an encounter with HIV? And vaginal probiotics—living microbicides—could be created by genetically altering bacterial cultures such as the common lactobacilli.
Research is showing that HIV might lower the electrical barrier of epithelial cells, enabling infection even without surface damage. Such new knowledge could produce future strategies and modes of protection.
Copyright © 2011 Poz Magazine
by Trenton Straube
Rectal microbicides-topical gels, ointments and lubricants laced with ?drugs to block HIV-could help stop the spread of the virus. So why is it taking so long to develop them? For one thing, an unwillingness to talk about sex-especially anal sex. Given the potential of microbicides' protective power, it's time we loosen our tongues in order to start saving lives.
In 1992, at a meeting of the Delaware Valley Women and AIDS Network, Anna Forbes first heard about experimental compounds called vaginal microbicides. It sparked an “A-ha!” moment for the longtime advocate for women’s health. Forbes saw right away how a microbicide—a gel, cream, lubricant or other topical agent that could be applied to the vagina to inhibit sexual transmission of HIV—would offer a much-needed method of protection to women, especially those who couldn’t get their partners to use condoms. And as an advocate for gay men’s health, Forbes also imagined how a rectal microbicide could offer a valuable prevention tool for anal sex for both men and women.
Women and gay men share the common concern of having their health needs respected and addressed, Forbes says. “A receptive partner is a receptive partner.” Effective microbicides would arm both male and female receptive partners with prevention tools that could save their lives.
But when she started talking about the notion of vaginal and rectal microbicides, Forbes found that even people on the cutting edge of women’s and gay men’s health advocacy were uncomfortable talking so specifically about sex, especially anal sex. It showed, according to Forbes, “this weird way that homophobia and sexism intersected.” And it pointed out “the well-kept secret that women have anal sex too.”
Undaunted by the reluctance of many of her peers, and inspired by the potential lifesaving power of microbicides, Forbes set out to convince the world to think similarly, working for a decade at the Global Campaign for Microbicides (she recently moved into consulting). The topic continued to be a hard sell. “The trouble with microbicides in comparison to pills and injections,” Forbes says, “is that they are applied ‘down there.’ You can’t talk about microbicides without talking about sex.”
Thanks in part to the unflagging efforts of Forbes and other visionary leaders (along with increasingly promising research data), the scientific and advocacy communities began rallying around vaginal microbicide research. Yet, very few people supported the notion of a rectal version. Forbes recalls the first time she saw the topic discussed in the print media, in a 1999 POZ article, “Beyond Condoms: Life After Latex,” in which journalist Michael Scarce presciently wrote: “The astonishing thing is, gay men raise no voice to advocate for a form of HIV prevention that maximizes pleasure and safety.” In Colorado the next year, at the second LGBTI Health Summit (the initials embrace lesbian, gay, bisexual, trans and intersex people), Forbes gave a presentation on the need for rectal microbicides. Only about five people showed up. Clearly, interest in the subject was lacking—even among the most likely benefactors, gay men.
Then, another A-ha! moment: The messenger, Forbes realized, needed to double as the message. A straight woman couldn’t draw the same attention in the gay community as a gay man could. “We needed a gay male face, somebody with a track record in the [prevention] field,” she says. She envisioned an organized group led by a gay man working to promote rectal microbicides and in the process tackling the taboos associated with anal sex. In 2005, Forbes approached some likely advocates: Marc-André LeBlanc from the Canadian AIDS Society, Julie Davids from CHAMP (Community HIV/AIDS Mobilization Project) and Jim Pickett of the AIDS Foundation of Chicago. Although all were overextended, they agreed on the need to fight for a new form of prevention. Thus, the International Rectal Microbicide Advocates (IRMA) group was formed.
IRMA began modestly. “We had a listserv, and our goal was to get people to share information [about rectal microbicides],” says Pickett, IRMA’s chair (its out, gay face). He recalls begging people at the 2005 National HIV Prevention Conference to join the email group. Many resisted, arguing that rectal microbicides were too futuristic and that advocating for them would deflect resources from the priority concern at the moment: condoms. “People would almost groan when Jim would get on stage,” says Ian McGowan, MD, a leading microbicide researcher.
People’s reluctance to talk about butts (male and female), similarly muzzled scientists. As recently as a few years ago, many researchers scoffed at the very idea of a rectal microbicide, claiming human anatomy made it impossible. Unlike the vagina, which is essentially an enclosed container, the five-foot-long colon, Pickett says, is “like the Holland Tunnel.” There was the question of how far ejaculate could travel up the colon. Would the colon’s entire surface have to be protected? How much gel would be required—and how much could a body take? Scientists didn’t know. That is, until Craig Hendrix, MD, at Johns Hopkins University, conducted experiments involving some brave volunteers, faux microbicides and a hollow dildo that squirted an “ejaculate” traceable by MRI scans. (Read one volunteer’s hilarious account, “Putting My Ass on the Line,” on the IRMA blog at irma-rectalmicrobicides.blogspot.com.)The experiments proved that the faux microbicide traveled well with the ejaculate and that to be effective, a microbicide would likely need to coat only the lowest 4 to 6 inches of the rectum and anal canal. Furthermore, researchers determined that ?humans could tolerate up to 30 milliliters (ml) of gel administered anally. However, the gel currently being studied requires only 4 ml, less than a teaspoon.
If these details make you squirm, you wouldn’t want Pickett’s job. The gregarious advocate constantly finds himself discussing anal sex and all its details—often in front of crowds. He does so as easily as most guys rattle off sports stats, employing honesty and humor that prove disarming. Equally important, he and IRMA back up their cause with something scientists recognize: cold, hard data.
Perhaps IRMA’s most visible work is three game-changing reports it published in conjunction with the biennial International Microbicides Conference. The first, Rectal Microbicides: Investments & Advocacy in 2006, compiled what research was being done and where—a tricky task. “A lot of researchers were concerned that if ‘anal’ or ‘rectal’ appeared in research proposals or reports, they wouldn’t get funded, so they’d scrub their papers so those words wouldn’t show up,” LeBlanc says. “Instead, they would refer to ‘topical use of products’ or other language.” And because of the dangers surrounding the subject—male-to-male sex is illegal in many countries, including 31 in sub-Saharan Africa—IRMA first had to gain researchers’ trust, proving they were not raging advocates who would alienate and antagonize. Their professionalism paid off, and the report was a hit. “It showed we were serious,” Pickett says, “and we got hundreds of new members.”
The next two reports, Less Silence, More Science in 2008 and From Promise to Product: Advancing Rectal Microbicide Research and Advocacy in 2010 (all the reports are available at rectalmicrobicides.org), addressed the reality that anal sex is more common than believed. The reports showed that among women anal sex remains an overlooked driver of the AIDS epidemic. (Because there are more women in the world than gay men, the overall number of women having receptive anal sex is higher than that of gay men.) By amassing data and research from across the globe, the reports argue effectively for developing rectal microbicides. A sampling from the 2010 report:
- It is estimated that unprotected anal intercourse transmits HIV 10 to 20 times more effectively than unprotected vaginal intercourse.
- Gay men in the developing world are 19 times more likely to be positive compared with the general population.
- In the United States, men who have sex with men (MSM) represent 53 percent of new HIV infections.
- Depending on the study, 20 to 75 percent of women report having engaged in receptive anal sex.
- Globally, up to seven times more women than men have receptive anal sex.
Beyond advocacy and education about anal sex, IRMA helps shape a unified research agenda, coordinating studies among disparate, often unconnected researchers across the globe. (“We herd the cats,” Pickett says.) It directs funds to needed areas (though it doesn’t directly fund research). It digests complex research into talking points for mainstream media, translates reports into other languages, asks important questions and pursues answers.
Along the way, microbicide research has produced some immediate benefits. At a 2006 Cape Town AIDS conference, biomedical scientists with the Population Council presented data on the possible link between anal lubes and HIV risk. (The same team, lead by David Phillips, PhD, reported in 2000 that the spermicide nonoxynol-9 damaged linings of the rectum and vagina, thus increasing the risk for HIV and herpes—findings that resulted in N-9 being removed from most condoms.) The lube presentation, Pickett says, sparked his own revelatory moment. “We were like, The lubes we have are not tested for safety? We have to get research on this. Yes, we want rectal microbicides, but people are using lubes today!”
At the time, little was known about the popularity, use and safety of anal lubes—in the United States, lubes must be tested for vaginal irritation (in rabbits) but not for rectal use. To build a research database, IRMA conducted a survey. “We thought we’d get a few dozen answers,” LeBlanc says, “but we had nearly 9,000 people respond from nearly 100 countries.” The survey was translated into six languages. “As far as we know, it’s the largest survey on anal sex in the world.” (IRMA is following up with a survey on douches and enemas, which might affect HIV/STI risk and offer a mode of microbicide delivery.)
The survey results have been pivotal to researchers such as Charlene Dezzutti, PhD, a lab director at the Microbicide Trials Network, who is examining the lube qualities that might affect HIV risk and be of use in microbicides. (For more on lube safety and her findings, see "Slippery Slopes," on the following page.)
IRMA’s hard work is paying off elsewhere too. The energetic listserv now includes more than 1,000 members. Pickett manages its daily conversation from his office at the AIDS Foundation of Chicago (AFC), where he is director of advocacy (IRMA is a project of AFC). “I think the overarching thing that has made us successful is that we bring together scientists and advocates,” Pickett says. “There is no other forum like this. An advocate in Thailand can post an opinion, and a researcher in Peru or London or Pittsburgh can comment all in the same hour—people find it really useful.”
Discussions range across prevention topics including study results, female condoms and Uganda’s Anti-Homosexuality Bill. One round of emails discussed a British safe-sex musical video with the problematic lyrics, “Something to remember as a rule of thumb, one up the bum and there’s no harm done…one up the bum and you won’t be a mum.” (Listserv members contacted the video’s creators to argue against promoting anal intercourse as a risk-free way to avoid getting pregnant.)
“[IRMA is] doing all the right stuff,” says Forbes, speaking like a proud momma. “They’re recognizing the importance of geographic and constituency diversities, and they’re promoting everybody having the discussion in whatever way makes sense in their own communities and encouraging people to share ownership—exactly what we need.”
This year, IRMA had good news to trumpet. A Microbicide Trials Network study, MTN-006, found that people who used a rectal gel containing 1 percent tenofovir, an HIV drug, had high concentrations of the med in rectal tissue and lower concentrations in the blood stream, which could mean fewer side effects. The downside: A single dose before sex probably won’t be effective.
Today, people no longer groan when Pickett takes the stage. “People came up to me after the CAPRISA results [a large South African microbicide study] and said, ‘For all these years, I thought you were crazy, but you’ve proven me wrong. Now I understand why you had such a belief in this.’”
Perhaps IRMA’s biggest success is simply getting people to confront the realities of anal sex and HIV. Because without honest dialogue about sex—whether at an international science conference, a sex education class or an intimate chat between lovers—we are never going to stop this epidemic. And that’s something we all need to speak up for.
Slippery Slopes
Can lubes increase the risk of HIV during anal sex?
A slew of recent studies suggest that using lubes for unprotected anal sex may increase the risk of HIV, and that some lubes may harm the rectum’s thin protective layer of cells (the epithelium). It’s premature to know which brands to avoid, says Marc-André LeBlanc, a lube advocate with the International Rectal Microbicide Advocates (IRMA). Most research has been done in laboratories, and it isn’t certain whether the findings translate to humans—or whether the products’ lubricating benefits outweigh their potential harm. But one fact is certain: “The best way to prevent acquiring HIV and STIs [sexually transmitted infections] during anal sex is still using male or female condoms,” LeBlanc says. “And we know that using lubes with condoms decreases the risk of the condom slipping or breaking—a big bonus.”
In the meantime, here’s a highlight of what scientists are investigating and how lube qualities might affect the success of microbicides:
- Polyquaterniums, a class of chemicals common in cosmetics, seem to increase HIV replication by almost four times in lab tests. A Population Council study found this ingredient in three of four HIV-enhancing Astroglide brand lubes: Astroglide Liquid, Astroglide Warming Liquid, Astroglide Glyercin & Paraben Free liquid and Astroglide Silken Secret.
- Osmolality refers to the concentration of salts, sugars and other substances (solutes) present in a lube. Hypo-osmolar lubes have a lower concentration of solutes than human cells and cause the cells to swell with water and burst. Hyperosmolar lubes cause cells to shrink and become brittle. Iso-osmolar lubes don’t affect cells because their concentrations are identical.
- Most water-based lubes are hyperosmolar and damaging.
- pH balance is acidic in the vagina and neutral in the rectum. Many lubes are designed for the vagina—does the difference in pH mean they affect the rectum differently?
- Good and bad bacteria live in a delicate balance in the vagina and gut. Will disrupting this balance make the rectum more susceptible to HIV?
- Viscosity is the slippery quality that gives lube its feel and texture. Glycerin, in water-based lubes, adds to viscosity. It also makes lubes hyperosmolar—and destructive to epithelium. When a rectal microbicide now in trials proved harmful to the epithelium, researchers solved the problem by lowering the glycerin content.
Starting to Gel
Microbicides: Where they are now and where they are going
VAGINAL GEL: After two decades of disappointing results, a breakthrough arrived last summer with results of the CAPRISA 004 trial: Women using a gel containing 1 percent tenofovir (an HIV med found in Atripla, Viread and Truvada) had 39 percent fewer infections than those using a placebo. Women with 80 percent adherence to the two necessary applications per sex act (12 hours before, then immediately after) had even fewer infections. The gel also offered protection against herpes.
What’s Next: Studies are under-way to confirm CAPRISA 004 results and determine the most effective concentrations and doses, but the global economic crisis has depleted funding, slowing progress. On the bright side, the drug from the vaginal gel is showing up in rectal tissue, so one product might offer women protection in both areas.
RECTAL GEL: Microbicide Trials Network study MTN-006 looked at using the vaginal tenofovir gel rectally, with promising results announced in February. Although the vaginal formulation harmed the rectal lining and caused gastrointestinal distress, Charlene Dezzutti’s team developed a better version with less glycerin. And, says Ian McGowan, PhD, a co-principal study investigator, “We found that when you give the drug topically, you get very high concentrations in the rectal tissue—a hundred times the amount from a single Viread tablet.” A few caveats: Tenofovir works not by directly attacking and disarming HIV, but by accumulating in the tissue and CD4 cells HIV will attack, preventing HIV from replicating once it invades the cell. Unfortunately, this accumulation demands repeated doses. “I think MTN-006 suggests,” McGowan says, “that if you just take one dose, orally or rectally, half an hour before exposure, I would doubt you’d be protected.”
What’s Next: A Phase I study (MTN-007) on the safety and acceptability of the rectal tenofovir gel; and Project Gel, investigating the use of rectal microbicides among African-American and Latino men who have sex with men (MSM). “It’s critical,” McGowan says, “because these are the people who are getting infected and need the product.”
FUTURE IDEAS AND EXPERIMENTS:
Other HIV meds or combos—or completely new compounds—may offer better protection than tenofovir as microbicides (hint: HIV drugs that are too toxic as pills may work as topical solutions).
Different modes of delivery: How about a slowly dissolving ring instead of a vaginal gel? Or combining a microbicide with a vaccine, to help prepare the immune system for an encounter with HIV? And vaginal probiotics—living microbicides—could be created by genetically altering bacterial cultures such as the common lactobacilli.
Research is showing that HIV might lower the electrical barrier of epithelial cells, enabling infection even without surface damage. Such new knowledge could produce future strategies and modes of protection.
Copyright © 2011 Poz Magazine
Friday, July 08, 2011
Maraviroc Abacavir STudy - Effect on Endothelial Recovery
HIV infected patients treated with abacavir might have a higher risk for the occurrence of cardiovascular events. At time of writing of this protocol the underlying mechanism is not yet elucidated, however some studies find impaired endothelial function and elevated markers of chronic inflammation in these patients,suggesting a higher lever of chronic inflammation. Recently maraviroc...
Brief Summary
Official Title: “Maraviroc Abacavir STudy - Effect on Endothelial Recovery”
HIV infected patients treated with abacavir might have a higher risk for the occurrence of cardiovascular events. At time of writing of this protocol the underlying mechanism is not yet elucidated, however some studies find impaired endothelial function and elevated markers of chronic inflammation in these patients,suggesting a higher lever of chronic inflammation.
Recently maraviroc (Celsentri®), a CCR5-receptor antagonist, became available for treatment of patients infected with HIV-1.
Improvement of endothelial function may be a potential beneficial side effect of treatment with maraviroc, due to the potential reduction of immune activation and chronic inflammation as a result of blocking the CCR5-coreceptor. Moreover, treatment intensification of HAART with maraviroc in patients with suppressed plasma HIV_RNA may decrease plasma HIVRNA below the cut-off of 50 copies/ml as well.
The investigators hypothesize that maraviroc intensification therapy in patients on an abacavir-containing regimen will improve endothelial function.
The objectives of this study are: First, to assess the effect of addition of maraviroc to an abacavir-containing regimen on endothelial function; second, to assess the effect of this intervention on markers of immune activation and chronic inflammation, and on plasma HIV-RNA below 50 copies/ml.
Study Type: Interventional
Study Design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Study Primary Completion Date: September 2012
Detailed Clinical Trial Description
The MASTER study is a phase IV, randomized, open label, cross-over, intervention study.
Study subjects who are on stable abacavir-containing regimen will be randomized into two arms. In arm A maraviroc will be added to their regimen at baseline, while study subjects in arm B will continue their abacavir-containing regimen. After 8 weeks, cross-over of the study arms will be performed. Subjects in arm A will then stop maraviroc, while in subjects in arm B maraviroc will be added to their regimen (for 8 weeks again). The total duration of the study will be 16 weeks.
Intervention(s) in this Clinical Trial
Drug: Maraviroc
HAART of subjects enrolled in arm A will be intensified with maraviroc during week 1-8.
Arms, Groups and Cohorts in this Clinical Trial
Active Comparator: Arm A
HAART of subjects in arm A will be intensified with maraviroc during week 1-8.
Active Comparator: Arm B
HAART of subjects enrolled in arm B will be intensified with maraviroc during week 9-16
Outcome Measures for this Clinical Trial
Primary Measures
Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks of maraviroc treatment as compared to the control group
Time Frame: After 8 weeks of treatment (cross-over)
Safety Issue?: No
Secondary Measures
Change in markers of chronic inflammation
Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16
Safety Issue?: No
Change in markers of immune activation
Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16
Safety Issue?: No
Change in markers of endothelial function
Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16
Safety Issue?: No
Changes in plasma HIV-RNA below 50 copies/ml
Time Frame: Baseline, week 8, week 16
Safety Issue?: No
Change in endothelial function measured by EndoPAT
Time Frame: baseline, week 8, week 16
Safety Issue?: No
Criteria for Participation in this Clinical Trial
Inclusion Criteria:
Age > 18 years
HIV-1 infection
Treatment with antiretroviral regimen containing abacavir for at least the previous 3 months
Undetectable plasma HIV RNA (50 cp/ml) for at least 6 months (one 'blip' allowed, which is defined as a detectable plasma HIV-RNA level between 50 and 400 copies/ml, preceded and followed by undetectable (<50 copies/ml) plasma HIV-RNA measurements) CD4+ cell count > 200 cells/µL
Signed informed consent
Exclusion Criteria:
Pregnancy
Breastfeeding
Allergy for peanuts or soya
Hypersensitivity for maraviroc
Treatment of underlying malignancy
Acute infection in the preceding 30 days
Renal insufficiency requiring hemodialysis
Acute or decompensated chronic hepatitis
Modification of antiretroviral regimen in the previous 3 months
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Investigator Information
Lead Investigator: UMC Utrecht Other
Overall Clinical Trial Officials and Contacts
A IM Hoepelman, MD, PhD Principal Investigator UMC Utrecht
Overall Contact: Steven FL van Lelyveld, MD s.f.l.vanlelyveld@umcutrecht.nl
Additional Information
Information obtained from ClinicalTrials.gov on July 06, 2011
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01389063
Study ID Number: MASTER2010
ClinicalTrials.gov Identifier: NCT01389063
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Copyright © 2011 ClinicalTrials
HIV infected patients treated with abacavir might have a higher risk for the occurrence of cardiovascular events. At time of writing of this protocol the underlying mechanism is not yet elucidated, however some studies find impaired endothelial function and elevated markers of chronic inflammation in these patients,suggesting a higher lever of chronic inflammation. Recently maraviroc...
Brief Summary
Official Title: “Maraviroc Abacavir STudy - Effect on Endothelial Recovery”
HIV infected patients treated with abacavir might have a higher risk for the occurrence of cardiovascular events. At time of writing of this protocol the underlying mechanism is not yet elucidated, however some studies find impaired endothelial function and elevated markers of chronic inflammation in these patients,suggesting a higher lever of chronic inflammation.
Recently maraviroc (Celsentri®), a CCR5-receptor antagonist, became available for treatment of patients infected with HIV-1.
Improvement of endothelial function may be a potential beneficial side effect of treatment with maraviroc, due to the potential reduction of immune activation and chronic inflammation as a result of blocking the CCR5-coreceptor. Moreover, treatment intensification of HAART with maraviroc in patients with suppressed plasma HIV_RNA may decrease plasma HIVRNA below the cut-off of 50 copies/ml as well.
The investigators hypothesize that maraviroc intensification therapy in patients on an abacavir-containing regimen will improve endothelial function.
The objectives of this study are: First, to assess the effect of addition of maraviroc to an abacavir-containing regimen on endothelial function; second, to assess the effect of this intervention on markers of immune activation and chronic inflammation, and on plasma HIV-RNA below 50 copies/ml.
Detailed Clinical Trial Description
The MASTER study is a phase IV, randomized, open label, cross-over, intervention study.
Study subjects who are on stable abacavir-containing regimen will be randomized into two arms. In arm A maraviroc will be added to their regimen at baseline, while study subjects in arm B will continue their abacavir-containing regimen. After 8 weeks, cross-over of the study arms will be performed. Subjects in arm A will then stop maraviroc, while in subjects in arm B maraviroc will be added to their regimen (for 8 weeks again). The total duration of the study will be 16 weeks.
Intervention(s) in this Clinical Trial
Drug: Maraviroc
HAART of subjects enrolled in arm A will be intensified with maraviroc during week 1-8.
Arms, Groups and Cohorts in this Clinical Trial
Active Comparator: Arm A
HAART of subjects in arm A will be intensified with maraviroc during week 1-8.
Active Comparator: Arm B
HAART of subjects enrolled in arm B will be intensified with maraviroc during week 9-16
Outcome Measures for this Clinical Trial
Primary Measures
Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks of maraviroc treatment as compared to the control group
Time Frame: After 8 weeks of treatment (cross-over)
Safety Issue?: No
Secondary Measures
Change in markers of chronic inflammation
Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16
Safety Issue?: No
Change in markers of immune activation
Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16
Safety Issue?: No
Change in markers of endothelial function
Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16
Safety Issue?: No
Changes in plasma HIV-RNA below 50 copies/ml
Time Frame: Baseline, week 8, week 16
Safety Issue?: No
Change in endothelial function measured by EndoPAT
Time Frame: baseline, week 8, week 16
Safety Issue?: No
Criteria for Participation in this Clinical Trial
Inclusion Criteria:
Age > 18 years
HIV-1 infection
Treatment with antiretroviral regimen containing abacavir for at least the previous 3 months
Undetectable plasma HIV RNA (50 cp/ml) for at least 6 months (one 'blip' allowed, which is defined as a detectable plasma HIV-RNA level between 50 and 400 copies/ml, preceded and followed by undetectable (<50 copies/ml) plasma HIV-RNA measurements) CD4+ cell count > 200 cells/µL
Signed informed consent
Exclusion Criteria:
Pregnancy
Breastfeeding
Allergy for peanuts or soya
Hypersensitivity for maraviroc
Treatment of underlying malignancy
Acute infection in the preceding 30 days
Renal insufficiency requiring hemodialysis
Acute or decompensated chronic hepatitis
Modification of antiretroviral regimen in the previous 3 months
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Investigator Information
Lead Investigator: UMC Utrecht Other
Overall Clinical Trial Officials and Contacts
A IM Hoepelman, MD, PhD Principal Investigator UMC Utrecht
Overall Contact: Steven FL van Lelyveld, MD s.f.l.vanlelyveld@umcutrecht.nl
Additional Information
Information obtained from ClinicalTrials.gov on July 06, 2011
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01389063
Study ID Number: MASTER2010
ClinicalTrials.gov Identifier: NCT01389063
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Copyright © 2011 ClinicalTrials
Thursday, July 07, 2011
CD4s Above 500: HIV Treatment Need Still Unclear
If you’re diagnosed with HIV and have a CD4 cell count above 500, should you start antiretroviral (ARV) therapy immediately? An Australian study suggests that even though there may be some immunologic benefits to starting therapy earlier than is currently recommended—once the CD4 count drops below 500—the jury is still out on whether this translates into important clinical benefits.
Despite more than 25 years of ARV research and the successful development of more than two dozen medications, scientists have not been able to determine the ideal time to begin therapy. Several studies have concluded that HIV treatment is best started before a person’s CD4 count falls below 350.
Some studies, conducted during the past five years, suggest that starting therapy even earlier—when the CD4 count is between 350 and 500—further increases the chances of disease-free survival. Less is known about the potential benefits of initiating therapy earlier still, when the CD4 count is above 500.
A large clinical trial, called the Strategic Timing of Antiretroviral Treatment (START) study, is being conducted to explore the safety and effectiveness of beginning treatment when the CD4 count is above 350 cells. Preliminary data, however, are not expected for at least another few years.
In the meantime, HIV-positive people and their health care providers are on the lookout for smaller observational and retrospective studies, such as the one recently published online by the Journal of Acquired Immune Deficiency Syndromes and based on data from Stephen Wright and his colleagues with the Australian HIV Observational Database.
Wright’s group looked at the outcomes of 432 people living with HIV who started ARV therapy with a CD4 count above 350 and had been followed for six years (72 months). For their analysis, the researchers divided the study volunteers into three groups: those who started treatment with a CD4 count between 350 and 500, those who started treatment with a CD4 count between 501 and 650 and those who started treatment with a CD4 count above 650.
Twelve months after beginning treatment, all study volunteers had CD4s above 500. Average CD4 counts, after a year of ARV therapy, were 596 among those who started with CD4s between 250 and 500, 717 among those who started treatment with CD4s between 501 and 650, and 881 among those who started treatment with a CD4 count in excess of 650.
After six years, CD4 counts were comparable between the three groups. Among those in the lowest pre-treatment CD4 group, the average CD4 cell count was 689. In the middle- and high-pretreatment CD4 groups, the average CD4 count after three years was 746 and 742, respectively.
Wright’s team also sought to determine whether there was a survival advantage between the three groups. Comparing their Australian data with those of another study, the researchers documented a modest 8 percent expected reduction in the risk of death among those who started treatment with more than 650 CD4s and a 4 percent expected reduction in the risk of death among those who started treatment with 501 to 650 CD4s, compared with those who started treatment with CD4s between 350 and 500. It is important to note, however, that the estimated number of deaths in these three groups were very low, which translated into very small differences in the absolute risk of death between those in the two highest CD4 groups compared with those starting with CD4s between 350 and 500.
“Our analysis suggests that patients who start [ARV therapy] at CD4 counts [greater than] 650 have better preserved immune function, but only to a relatively modest degree,” the authors conclude. “Furthermore the extent to which this might be expected to result in better clinical outcomes is uncertain.”
Copyright © 2011 AIDSmeds
If you’re diagnosed with HIV and have a CD4 cell count above 500, should you start antiretroviral (ARV) therapy immediately? An Australian study suggests that even though there may be some immunologic benefits to starting therapy earlier than is currently recommended—once the CD4 count drops below 500—the jury is still out on whether this translates into important clinical benefits.
Despite more than 25 years of ARV research and the successful development of more than two dozen medications, scientists have not been able to determine the ideal time to begin therapy. Several studies have concluded that HIV treatment is best started before a person’s CD4 count falls below 350.
Some studies, conducted during the past five years, suggest that starting therapy even earlier—when the CD4 count is between 350 and 500—further increases the chances of disease-free survival. Less is known about the potential benefits of initiating therapy earlier still, when the CD4 count is above 500.
A large clinical trial, called the Strategic Timing of Antiretroviral Treatment (START) study, is being conducted to explore the safety and effectiveness of beginning treatment when the CD4 count is above 350 cells. Preliminary data, however, are not expected for at least another few years.
In the meantime, HIV-positive people and their health care providers are on the lookout for smaller observational and retrospective studies, such as the one recently published online by the Journal of Acquired Immune Deficiency Syndromes and based on data from Stephen Wright and his colleagues with the Australian HIV Observational Database.
Wright’s group looked at the outcomes of 432 people living with HIV who started ARV therapy with a CD4 count above 350 and had been followed for six years (72 months). For their analysis, the researchers divided the study volunteers into three groups: those who started treatment with a CD4 count between 350 and 500, those who started treatment with a CD4 count between 501 and 650 and those who started treatment with a CD4 count above 650.
Twelve months after beginning treatment, all study volunteers had CD4s above 500. Average CD4 counts, after a year of ARV therapy, were 596 among those who started with CD4s between 250 and 500, 717 among those who started treatment with CD4s between 501 and 650, and 881 among those who started treatment with a CD4 count in excess of 650.
After six years, CD4 counts were comparable between the three groups. Among those in the lowest pre-treatment CD4 group, the average CD4 cell count was 689. In the middle- and high-pretreatment CD4 groups, the average CD4 count after three years was 746 and 742, respectively.
Wright’s team also sought to determine whether there was a survival advantage between the three groups. Comparing their Australian data with those of another study, the researchers documented a modest 8 percent expected reduction in the risk of death among those who started treatment with more than 650 CD4s and a 4 percent expected reduction in the risk of death among those who started treatment with 501 to 650 CD4s, compared with those who started treatment with CD4s between 350 and 500. It is important to note, however, that the estimated number of deaths in these three groups were very low, which translated into very small differences in the absolute risk of death between those in the two highest CD4 groups compared with those starting with CD4s between 350 and 500.
“Our analysis suggests that patients who start [ARV therapy] at CD4 counts [greater than] 650 have better preserved immune function, but only to a relatively modest degree,” the authors conclude. “Furthermore the extent to which this might be expected to result in better clinical outcomes is uncertain.”
Copyright © 2011 AIDSmeds
Wednesday, July 06, 2011
Physicians urge FDA not to approve Truvada
Alaric Dearment
LOS ANGELES — A group of physicians is urging the Food and Drug Administration not to approve a drug made by Gilead Sciences for the prevention of HIV infection.
Fifty-five physicians signed a letter spearheaded by the AIDS Healthcare Foundation citing concerns about the use of Gilead’s Truvada (tenofovir disoproxil fumarate and emtricitabine) for “pre-exposure prophylaxis,” or PrEP. Concerns included the risk of a decrease in condom use and a lack of information showing proper use in “real world” situations.
“As medical care providers, we strongly support continued research on the prevention of HIV, but oppose approval of a pre-exposure prophylaxis that runs the risk of contributing to the spread of HIV and drug-resistant viruses,” the physicians wrote. “Our first obligation is to do no harm to individuals and to the public health.”
Copyright © 2011 Drug Store News
Alaric Dearment
LOS ANGELES — A group of physicians is urging the Food and Drug Administration not to approve a drug made by Gilead Sciences for the prevention of HIV infection.
Fifty-five physicians signed a letter spearheaded by the AIDS Healthcare Foundation citing concerns about the use of Gilead’s Truvada (tenofovir disoproxil fumarate and emtricitabine) for “pre-exposure prophylaxis,” or PrEP. Concerns included the risk of a decrease in condom use and a lack of information showing proper use in “real world” situations.
“As medical care providers, we strongly support continued research on the prevention of HIV, but oppose approval of a pre-exposure prophylaxis that runs the risk of contributing to the spread of HIV and drug-resistant viruses,” the physicians wrote. “Our first obligation is to do no harm to individuals and to the public health.”
Copyright © 2011 Drug Store News
How Much Is a Drug-Resistance Death Worth? Less Than $600
By Maryn McKenna
So, antibiotic resistance: We care about it, right? The World Health Organization does: It made antimicrobial resistance the theme of this year’s World Health Day. The Centers for Disease Control and Prevention does. The journal Lancet Infectious Diseases says it’s a “global health concern.” The major association for infectious disease physicians has pleaded for attention. Two separate sets of legislators have introduced two bills in Congress.
You’d think, with all those calls for attention, that combating antibiotic resistance would be a priority in the United States. But if we can take how much we spend to research a problem as a gauge of how much we care about it, then antibiotic resistance is no priority at all.
As in: For every death from AIDS, the US federal research establishment awards approximately $69,000 in grant funds. And for every death from MRSA, it awards $570.
The numbers come from an analysis presented at the World HAI Forum by Dr. Eli Perencevich of the University of Iowa (and the blog Controversies in Hospital Infection Prevention) and co-authors S. Kwon and M.L. Schweizer. (As far as I can tell, their poster is not online; perhaps they’ll post on it?)
As researchers competing for grants, they noted that the research budget at the National Institutes of Health has been rising, from $13.1 billion in 1998 to $28.7 billion in 2008; within that, so has the research budget at NIH’s National Institute of Allergy and Infectious Diseases (NIAID), from $1.4 billion to $4.6 billion over that same decade. They wondered how much of that research funding was going to this resistance problem that health authorities nationally and globally have pronounced a crisis. MRSA, let’s remember, kills an estimated 19,000 Americans a year: more than HIV, and more than pneumococcal disease, meningococcal disease, H. influenzae and group A Streptococcus combined.
They found the answer to be: Not very much.
To derive that answer, they drilled down into NIH’s Research Portfolio Online Reporting Tools database, RePORT for short, looking for all the grants awarded by NIAID that went to antibiotic resistance, antimicrobial resistance or hospital-associated infections. They especially looked for grants aimed at the seven most important resistant pathogens, the ones that cause the most illness and death and for which there are few remaining drugs that work: the Enterobacter species, MRSA and other resistant staph, C. difficile, Acinetobacter baumanii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterococcus faecium, collectively known as ESCKAPE.
What they found looked, at first, to be encouraging: From 2007 to 2009, the amount per grant and the total amount awarded for those topics and pathogens had gone up. In 2007, the total was $180 million; in 2009, it was $398 million. But then they looked at what NIH awards for other infectious diseases, and at that point the picture was much less positive. In 2007, NIAID funding for HIV/AIDS was $1.24 billion.
Plotted against the 18,000 AIDS deaths that year, that came to $69,000 per death. Breaking the antibiotic resistance funding apart by pathogen, they compared the 2007 funding for MRSA and for C. diff, and for the 18,650 deaths from invasive MRSA and 6,372 deaths from C. diff. Per death, the funding for those organisms was $570 and $560.
I asked Perencevich to help me make sense of these numbers. He replied by pointing to the utter dearth of new drugs for resistant pathogens — and to the fact that, because HIV has been a research priority for most of the 30 years of its existence, research has brought forth thousands of antiviral compounds and drug combinations for treatment.
“That’s what funding can do,” he said. “We need a renewed focus on antibacterial drug discovery and infection prevention. Our take-home point is that we ought to bring to this the same vigor that we’ve brought to HIV.”
Copyright © 2011 Wired
By Maryn McKenna
So, antibiotic resistance: We care about it, right? The World Health Organization does: It made antimicrobial resistance the theme of this year’s World Health Day. The Centers for Disease Control and Prevention does. The journal Lancet Infectious Diseases says it’s a “global health concern.” The major association for infectious disease physicians has pleaded for attention. Two separate sets of legislators have introduced two bills in Congress.
You’d think, with all those calls for attention, that combating antibiotic resistance would be a priority in the United States. But if we can take how much we spend to research a problem as a gauge of how much we care about it, then antibiotic resistance is no priority at all.
As in: For every death from AIDS, the US federal research establishment awards approximately $69,000 in grant funds. And for every death from MRSA, it awards $570.
The numbers come from an analysis presented at the World HAI Forum by Dr. Eli Perencevich of the University of Iowa (and the blog Controversies in Hospital Infection Prevention) and co-authors S. Kwon and M.L. Schweizer. (As far as I can tell, their poster is not online; perhaps they’ll post on it?)
As researchers competing for grants, they noted that the research budget at the National Institutes of Health has been rising, from $13.1 billion in 1998 to $28.7 billion in 2008; within that, so has the research budget at NIH’s National Institute of Allergy and Infectious Diseases (NIAID), from $1.4 billion to $4.6 billion over that same decade. They wondered how much of that research funding was going to this resistance problem that health authorities nationally and globally have pronounced a crisis. MRSA, let’s remember, kills an estimated 19,000 Americans a year: more than HIV, and more than pneumococcal disease, meningococcal disease, H. influenzae and group A Streptococcus combined.
They found the answer to be: Not very much.
To derive that answer, they drilled down into NIH’s Research Portfolio Online Reporting Tools database, RePORT for short, looking for all the grants awarded by NIAID that went to antibiotic resistance, antimicrobial resistance or hospital-associated infections. They especially looked for grants aimed at the seven most important resistant pathogens, the ones that cause the most illness and death and for which there are few remaining drugs that work: the Enterobacter species, MRSA and other resistant staph, C. difficile, Acinetobacter baumanii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterococcus faecium, collectively known as ESCKAPE.
What they found looked, at first, to be encouraging: From 2007 to 2009, the amount per grant and the total amount awarded for those topics and pathogens had gone up. In 2007, the total was $180 million; in 2009, it was $398 million. But then they looked at what NIH awards for other infectious diseases, and at that point the picture was much less positive. In 2007, NIAID funding for HIV/AIDS was $1.24 billion.
Plotted against the 18,000 AIDS deaths that year, that came to $69,000 per death. Breaking the antibiotic resistance funding apart by pathogen, they compared the 2007 funding for MRSA and for C. diff, and for the 18,650 deaths from invasive MRSA and 6,372 deaths from C. diff. Per death, the funding for those organisms was $570 and $560.
I asked Perencevich to help me make sense of these numbers. He replied by pointing to the utter dearth of new drugs for resistant pathogens — and to the fact that, because HIV has been a research priority for most of the 30 years of its existence, research has brought forth thousands of antiviral compounds and drug combinations for treatment.
“That’s what funding can do,” he said. “We need a renewed focus on antibacterial drug discovery and infection prevention. Our take-home point is that we ought to bring to this the same vigor that we’ve brought to HIV.”
Copyright © 2011 Wired
Is a HIV vaccine a viable option and at what price? An economic evaluation of adding HIV vaccination into existing prevention programs in Thailand
This study aims to determine the maximum price at which HIV vaccination is cost-effective in the Thai healthcare setting. It also aims to identify the relative importance of vaccine characteristics and risk behavior changes among vaccine recipients to determine how they affect this cost-effectiveness.
Methods: A semi-Markov model was developed to estimate the costs and health outcomes of HIV prevention programs combined with HIV vaccination in comparison to the existing HIV prevention programs without vaccination.
The estimation was based on a lifetime horizon period (99 years) and used the government perspective. The analysis focused on both the general population and specific high-risk population groups.
The maximum price of cost-effective vaccination was defined by using threshold analysis; one-way and probabilistic sensitivity analyses were performed. The study employed an expected value of perfect information (EVPI) analysis to determine the relative importance of parameters and to prioritize future studies.
Results: The most expensive HIV vaccination which is cost-effective when given to the general population was 12,000 Thai baht (US$1=34 Thai baht in 2009).
This vaccination came with 70% vaccine efficacy and lifetime protection as long as risk behavior was unchanged post-vaccination. The vaccine would be considered cost-ineffective at any price if it demonstrated low efficacy (30%) and if post-vaccination risk behavior increased by 10% or more, especially among the high-risk population groups.
The incremental cost-effectiveness ratios were the most sensitive to change in post-vaccination risk behavior, followed by vaccine efficacy and duration of protection. The EVPI indicated the need to quantify vaccine efficacy, changed post-vaccination risk behavior, and the costs of vaccination programs.
Conclusions: The approach used in this study differentiated it from other economic evaluations and can be applied for the economic evaluation of other health interventions not available in healthcare systems.
This study is important not only for researchers conducting future HIV vaccine research but also for policy decision makers who, in the future, will consider vaccine adoption.
Author: Pattara LeelahavarongYot Teerawattananon Pitsaphun Werayingyong Chutima Akaleephan Nakorn Premsri Chawetsan Namwat Wiwat Peerapatanapokin Viroj Tangcharoensathien
Copyright © 2011 7th Space Interactive
This study aims to determine the maximum price at which HIV vaccination is cost-effective in the Thai healthcare setting. It also aims to identify the relative importance of vaccine characteristics and risk behavior changes among vaccine recipients to determine how they affect this cost-effectiveness.
Methods: A semi-Markov model was developed to estimate the costs and health outcomes of HIV prevention programs combined with HIV vaccination in comparison to the existing HIV prevention programs without vaccination.
The estimation was based on a lifetime horizon period (99 years) and used the government perspective. The analysis focused on both the general population and specific high-risk population groups.
The maximum price of cost-effective vaccination was defined by using threshold analysis; one-way and probabilistic sensitivity analyses were performed. The study employed an expected value of perfect information (EVPI) analysis to determine the relative importance of parameters and to prioritize future studies.
Results: The most expensive HIV vaccination which is cost-effective when given to the general population was 12,000 Thai baht (US$1=34 Thai baht in 2009).
This vaccination came with 70% vaccine efficacy and lifetime protection as long as risk behavior was unchanged post-vaccination. The vaccine would be considered cost-ineffective at any price if it demonstrated low efficacy (30%) and if post-vaccination risk behavior increased by 10% or more, especially among the high-risk population groups.
The incremental cost-effectiveness ratios were the most sensitive to change in post-vaccination risk behavior, followed by vaccine efficacy and duration of protection. The EVPI indicated the need to quantify vaccine efficacy, changed post-vaccination risk behavior, and the costs of vaccination programs.
Conclusions: The approach used in this study differentiated it from other economic evaluations and can be applied for the economic evaluation of other health interventions not available in healthcare systems.
This study is important not only for researchers conducting future HIV vaccine research but also for policy decision makers who, in the future, will consider vaccine adoption.
Author: Pattara LeelahavarongYot Teerawattananon Pitsaphun Werayingyong Chutima Akaleephan Nakorn Premsri Chawetsan Namwat Wiwat Peerapatanapokin Viroj Tangcharoensathien
Copyright © 2011 7th Space Interactive
Tuesday, July 05, 2011
People With HIV May Be More Prone To Nervous System Problems That Affect The Heart Rate
Results from a recent Danish study indicate that otherwise healthy HIV-positive individuals may have moderate dysfunction of the nervous system that affects the heart rate, even after years of antiretroviral therapy. In particular, the researchers found that people with HIV had significantly higher resting heart rates and lower heart rate variability compared to HIV-negative individuals.
Additionally, the moderate nervous dysfunction (known as autonomic dysfunction) was associated with higher blood sugar and cholesterol levels, although this was not the case for HIV-negative study participants.
Based on their results, the study authors recommended close monitoring and maintenance of blood sugar and cholesterol levels in people with HIV. They also suggested that further studies be conducted to understand why HIV-positive individuals might be more sensitive to the effects on the nervous system of changes in blood sugar and cholesterol levels.
Autonomic dysfunction is a malfunction of the body’s autonomic nervous system, which controls automatic functions such as heart rate, digestion, and perspiration. Autonomic dysfunction is linked to an increased risk of heart problems.
In particular, heart rate and heart rate variability, or how the time interval between heart beats varies, are linked to measures of congestive heart failure, damage from diabetes, and mortality risk after a heart attack. Normally the heart rate should vary according to certain signals from the body, such as respiration rate or stress levels; lower variability can indicate problems with the autonomic nervous system.
According to the study authors, results from previous studies have shown evidence of autonomic dysfunction in people with HIV, especially individuals with advanced HIV or AIDS. However, there have been few studies investigating autonomic dysfunction in HIV-positive individuals whose HIV is well controlled with antiretroviral therapy.
Although antiretrovirals have the potential to reduce damage to the nervous system caused by HIV, they have also been implicated in high cholesterol levels and pre-diabetes, which could themselves cause autonomic nervous system damage.
In this study, the authors investigated the presence of autonomic dysfunction, as measured by heart rate and heart rate variability, in HIV-positive individuals who had been on antiretroviral therapy for at least one year.
The study included 97 HIV-positive individuals and 52 age- and gender-matched HIV-negative individuals. Participants with HIV had been HIV positive for a median of 11 years and had taken antiretrovirals for a median of seven years; all but one had viral loads (amount of HIV in the blood) of less than 400 copies per milliliter.
None of the participants had any history of heart disease, diabetes, or were taking medication for high blood pressure.
In order to measure heart rate and heart rate variability, the researchers performed an electrocardiogram on each participant for 15 minutes after an initial 10-minute resting period.
The researchers found evidence of moderate autonomic dysfunction in the HIV-positive study group compared to the HIV-negative study group. In particular, HIV-positive participants had faster heart rates than HIV-negative participants, with the time between heartbeats an average of 77 milliseconds (about 8 percent) shorter.
In addition, the heart rate variability was around 10 percent lower in HIV-positive individuals compared to HIV-negative individuals.
Results also showed that the dysfunction was linked to higher blood sugar and cholesterol levels, but only in the HIV-positive participants.
There was no link between dysfunction and duration of HIV infection, viral load, CD4 (white blood cell) count, or duration or type of antiretroviral therapy.
For more information, please see the study in PLoS One.
Copyright © 2011 The AIDS Beacon
The Autonomic Nervous System. Part II. Dysfunctions
Disorders of the Autonomic Nervous System
Results from a recent Danish study indicate that otherwise healthy HIV-positive individuals may have moderate dysfunction of the nervous system that affects the heart rate, even after years of antiretroviral therapy. In particular, the researchers found that people with HIV had significantly higher resting heart rates and lower heart rate variability compared to HIV-negative individuals.
Additionally, the moderate nervous dysfunction (known as autonomic dysfunction) was associated with higher blood sugar and cholesterol levels, although this was not the case for HIV-negative study participants.
Based on their results, the study authors recommended close monitoring and maintenance of blood sugar and cholesterol levels in people with HIV. They also suggested that further studies be conducted to understand why HIV-positive individuals might be more sensitive to the effects on the nervous system of changes in blood sugar and cholesterol levels.
Autonomic dysfunction is a malfunction of the body’s autonomic nervous system, which controls automatic functions such as heart rate, digestion, and perspiration. Autonomic dysfunction is linked to an increased risk of heart problems.
In particular, heart rate and heart rate variability, or how the time interval between heart beats varies, are linked to measures of congestive heart failure, damage from diabetes, and mortality risk after a heart attack. Normally the heart rate should vary according to certain signals from the body, such as respiration rate or stress levels; lower variability can indicate problems with the autonomic nervous system.
According to the study authors, results from previous studies have shown evidence of autonomic dysfunction in people with HIV, especially individuals with advanced HIV or AIDS. However, there have been few studies investigating autonomic dysfunction in HIV-positive individuals whose HIV is well controlled with antiretroviral therapy.
Although antiretrovirals have the potential to reduce damage to the nervous system caused by HIV, they have also been implicated in high cholesterol levels and pre-diabetes, which could themselves cause autonomic nervous system damage.
In this study, the authors investigated the presence of autonomic dysfunction, as measured by heart rate and heart rate variability, in HIV-positive individuals who had been on antiretroviral therapy for at least one year.
The study included 97 HIV-positive individuals and 52 age- and gender-matched HIV-negative individuals. Participants with HIV had been HIV positive for a median of 11 years and had taken antiretrovirals for a median of seven years; all but one had viral loads (amount of HIV in the blood) of less than 400 copies per milliliter.
None of the participants had any history of heart disease, diabetes, or were taking medication for high blood pressure.
In order to measure heart rate and heart rate variability, the researchers performed an electrocardiogram on each participant for 15 minutes after an initial 10-minute resting period.
The researchers found evidence of moderate autonomic dysfunction in the HIV-positive study group compared to the HIV-negative study group. In particular, HIV-positive participants had faster heart rates than HIV-negative participants, with the time between heartbeats an average of 77 milliseconds (about 8 percent) shorter.
In addition, the heart rate variability was around 10 percent lower in HIV-positive individuals compared to HIV-negative individuals.
Results also showed that the dysfunction was linked to higher blood sugar and cholesterol levels, but only in the HIV-positive participants.
There was no link between dysfunction and duration of HIV infection, viral load, CD4 (white blood cell) count, or duration or type of antiretroviral therapy.
For more information, please see the study in PLoS One.
Copyright © 2011 The AIDS Beacon
The Autonomic Nervous System. Part II. Dysfunctions
Disorders of the Autonomic Nervous System
Monday, July 04, 2011
Reyataz side effect: Mononeuritis multiplex
A study of Mononeuritis multiplex among people who take Reyataz. The study is created by eHealthMe based on reports from FDA and user community.
On Jul, 4, 2011: 3,710 people reported to have side effects when taking Reyataz. Among them, 1 people (0.03%) has Mononeuritis Multiplex.
Copyright © 2011 eHealthMe
A study of Mononeuritis multiplex among people who take Reyataz. The study is created by eHealthMe based on reports from FDA and user community.
On Jul, 4, 2011: 3,710 people reported to have side effects when taking Reyataz. Among them, 1 people (0.03%) has Mononeuritis Multiplex.
Copyright © 2011 eHealthMe
Atazanavir/r exposure is associated with an increased rate of renal stones compared with efavirenz, lopinavir/r and darunavir/r
Authors: Rockwood N, Mandalia S, Bower M, Gazzard B, Nelson M
There have been no data presented on the relative rates of the development of renal stones (RS) in those receiving ritonavir boosted atazanavir (ATZ/r) when compared with other commonly used antiretrovirals (ARVs).
We compared the rate of development of RS in a cohort of HIV infected individuals attending the Chelsea and Westminster Hospital Foundation Trust exposed to ATZ/r with those exposed to efavirenz (EFV)/lopinavir/r (LPV/r) and darunavir/r (DRV/r) over a 45 month study period.
The rate of development of RS in the ATZ/r group(n?=?1206) compared to the EFV/LPV/r/DRV/r combined group (n?=?4449) was 7.3 [95%CI: 4.7-10.8] per 1000 patient years and 1.9 [95%CI: 1.2-2.8] per 1000 patient years (p?
When choosing a boosted protease inhibitor, ATZ/r RS should be considered as a potential co-morbidity.
Copyright © 2011 MedicineJournalFeeds
Authors: Rockwood N, Mandalia S, Bower M, Gazzard B, Nelson M
There have been no data presented on the relative rates of the development of renal stones (RS) in those receiving ritonavir boosted atazanavir (ATZ/r) when compared with other commonly used antiretrovirals (ARVs).
We compared the rate of development of RS in a cohort of HIV infected individuals attending the Chelsea and Westminster Hospital Foundation Trust exposed to ATZ/r with those exposed to efavirenz (EFV)/lopinavir/r (LPV/r) and darunavir/r (DRV/r) over a 45 month study period.
The rate of development of RS in the ATZ/r group(n?=?1206) compared to the EFV/LPV/r/DRV/r combined group (n?=?4449) was 7.3 [95%CI: 4.7-10.8] per 1000 patient years and 1.9 [95%CI: 1.2-2.8] per 1000 patient years (p?
When choosing a boosted protease inhibitor, ATZ/r RS should be considered as a potential co-morbidity.
Copyright © 2011 MedicineJournalFeeds
A glimmer of a path to an AIDS vaccine
By Michael Gerson
In the 3-D model on the computer screen, the AIDS virus resembles a deformed head of broccoli, its clustered surface constantly shifting. Researchers at the National Institutes of Health’s Vaccine Research Center attribute moral characteristics to their enemy; it is “deceptive” and “diabolical.” The virus is covered in a cloak of sugars that mimic natural proteins, making it invisible to the immune system. Its true nature is only revealed to the body when the virus needs to get into a cell — latching onto a protrusion and injecting its genetic poison with a spring-loaded harpoon. It protects itself by constantly changing its genetic sequence. A person infected by one version of the virus, in a matter of weeks, can carry a million small mutations.
During its 30-year march, the virus has infected 65 million human bodies. Thirty million men, women and children have died. There is not a single example of an infected person whose immune system cleared the virus from his or her body.
This is the largest challenge for the vaccine researcher. The immune system has effective responses to diseases such as polio, measles or smallpox. Many people recover and gain immunity. The body itself proves that a vaccine is possible. But there is no naturally protective response to the AIDS virus. Medical researchers have to do better than nature.
During the decade following the creation of the Vaccine Research Center by President Bill Clinton, scientists gained a better understanding of the virus. But their main discovery was how difficult it would be to defeat. There was not even a scientific route to a solution. “It was like the ancient Greeks looking for a path to the moon,” recalls structural biologist Peter Kwong.
An audit of the center in 2008 would have found billions of dollars spent on few answers. But scientific progress often comes fitfully. “You do the groundwork,” says Gary Nabel, director of the center, “and then it pops.” In 2009, there were two unrelated breakthroughs. A Thai vaccine trial managed to produce a small protective effect, though researchers did not know why. At about the same time, improved diagnostics found that 10 to 25 percent of people with HIV produce antibodies that neutralize the virus — though the response is too weak and too late to make a difference.
The virus, it turns out, is vulnerable in one place. There is a portion of its cloak that can’t shift and camouflage itself — the small area where the virus latches on to the target cell. An antibody with the same footprint as the cell can block the attachment.
Scientists at NIH have now cloned that antibody. Produced in large enough quantities, it can be injected. Testing is scheduled to start next year. But even if this approach works, injecting manufactured antibodies won’t be an immediately practical solution. A gram of the antibody, Nabel estimates, might cost $100 to produce. Perhaps 100 million people would need to be injected once a month. This approach would be prohibitively expensive until costs are dramatically reduced.
The greater hope is a vaccine that could be injected once or a few times, producing an immune response that gives sustained protection. “We want the body to be the manufacturing plant for the antibodies,” explains Nabel. Unlike the precedent of other vaccines, it isn’t possible to use a dead version of the virus to produce immunity. It may be necessary to break off just the vulnerable bit of the virus, then introduce it into the body to provoke the production of antibodies. “It is not a fictional idea,” Nabel assures me. But it hasn’t been done before.
In the short and medium terms, neither injected antibodies nor a vaccine will be a substitute for other forms of AIDS prevention. Large reductions in infection rates can be achieved through consistent condom use, behavior change and circumcision. The treatment of HIV-infected pregnant women with AIDS drugs can prevent transmission to their children. Microbicide gels are promising.
But researchers at NIH know that an effective vaccine would be a decisive defeat for their wily enemy. “Every day there are 7,000 new infections,” reflects Nabel. “If we do our work a day sooner, it would make a difference.”
The day that work is finished remains distant. But now, at least, there is a path to the moon.
Copyright © 2011 Washington Post
By Michael Gerson
In the 3-D model on the computer screen, the AIDS virus resembles a deformed head of broccoli, its clustered surface constantly shifting. Researchers at the National Institutes of Health’s Vaccine Research Center attribute moral characteristics to their enemy; it is “deceptive” and “diabolical.” The virus is covered in a cloak of sugars that mimic natural proteins, making it invisible to the immune system. Its true nature is only revealed to the body when the virus needs to get into a cell — latching onto a protrusion and injecting its genetic poison with a spring-loaded harpoon. It protects itself by constantly changing its genetic sequence. A person infected by one version of the virus, in a matter of weeks, can carry a million small mutations.
During its 30-year march, the virus has infected 65 million human bodies. Thirty million men, women and children have died. There is not a single example of an infected person whose immune system cleared the virus from his or her body.
This is the largest challenge for the vaccine researcher. The immune system has effective responses to diseases such as polio, measles or smallpox. Many people recover and gain immunity. The body itself proves that a vaccine is possible. But there is no naturally protective response to the AIDS virus. Medical researchers have to do better than nature.
During the decade following the creation of the Vaccine Research Center by President Bill Clinton, scientists gained a better understanding of the virus. But their main discovery was how difficult it would be to defeat. There was not even a scientific route to a solution. “It was like the ancient Greeks looking for a path to the moon,” recalls structural biologist Peter Kwong.
An audit of the center in 2008 would have found billions of dollars spent on few answers. But scientific progress often comes fitfully. “You do the groundwork,” says Gary Nabel, director of the center, “and then it pops.” In 2009, there were two unrelated breakthroughs. A Thai vaccine trial managed to produce a small protective effect, though researchers did not know why. At about the same time, improved diagnostics found that 10 to 25 percent of people with HIV produce antibodies that neutralize the virus — though the response is too weak and too late to make a difference.
The virus, it turns out, is vulnerable in one place. There is a portion of its cloak that can’t shift and camouflage itself — the small area where the virus latches on to the target cell. An antibody with the same footprint as the cell can block the attachment.
Scientists at NIH have now cloned that antibody. Produced in large enough quantities, it can be injected. Testing is scheduled to start next year. But even if this approach works, injecting manufactured antibodies won’t be an immediately practical solution. A gram of the antibody, Nabel estimates, might cost $100 to produce. Perhaps 100 million people would need to be injected once a month. This approach would be prohibitively expensive until costs are dramatically reduced.
The greater hope is a vaccine that could be injected once or a few times, producing an immune response that gives sustained protection. “We want the body to be the manufacturing plant for the antibodies,” explains Nabel. Unlike the precedent of other vaccines, it isn’t possible to use a dead version of the virus to produce immunity. It may be necessary to break off just the vulnerable bit of the virus, then introduce it into the body to provoke the production of antibodies. “It is not a fictional idea,” Nabel assures me. But it hasn’t been done before.
In the short and medium terms, neither injected antibodies nor a vaccine will be a substitute for other forms of AIDS prevention. Large reductions in infection rates can be achieved through consistent condom use, behavior change and circumcision. The treatment of HIV-infected pregnant women with AIDS drugs can prevent transmission to their children. Microbicide gels are promising.
But researchers at NIH know that an effective vaccine would be a decisive defeat for their wily enemy. “Every day there are 7,000 new infections,” reflects Nabel. “If we do our work a day sooner, it would make a difference.”
The day that work is finished remains distant. But now, at least, there is a path to the moon.
Copyright © 2011 Washington Post
HIV drugs can lead to premature ageing of mitochondrial DNA
By Mehmet Fidanboylu
New research has revealed that a group of generic anti-HIV drugs may be linked to premature ageing. The study, which was carried out by UK scientists at the Institute of Genetic Medicine at Newcastle University, could explain why people treated with this class of drugs sometimes show signs of age-related conditions, such as heart disease and dementia.
The researchers studied muscle cells taken from people with HIV who had previously taken drugs known as nucleoside analogue reverse-transcriptase inhibitors (NRTIs) and found that DNA in the mitochondria of their cells had accumulated a number of errors that was more comparable to healthy people 20 or 30 years older.
'The DNA in our mitochondria gets copied throughout our lifetimes and, as we age, naturally accumulates errors. We believe that these drugs accelerate the rate at which these errors build up', said Professor Patrick Chennery, who led the study, adding: 'Over the space of, say, ten years, a person's mitochondrial DNA may have accumulated the same amount of errors as a person who has natural aged twenty or thirty years'.
NRTIs were a major breakthrough in the battle against HIV when they were developed in the late 1980s. But side-effects such as premature ageing and frailty have meant that they have been replaced by a cocktail of more recent drugs. However, NRTIs are generally favoured over these new drugs in developing countries due to their lower costs.
Until now it has not been clear why NRTIs, which include AZT or zidovudine, have these side-effects. 'HIV clinics were seeing patients who had otherwise been successfully treated but who showed signs of being much older than their years. This was a real mystery', said Professor Chinnery, 'but colleagues recognised many similarities with patients affected by mitochondrial diseases... and referred them to our clinic'.
Defects in mitochondrial DNA are often seen in age-related conditions, although it is not yet known whether this is a cause or consequence of taking the drugs.
It was estimated in 2009 that 33.3 million people had HIV, and of these 22.5 million live in Africa. The researchers were keen to stress that while NRTIs do sometimes have side-effects, not taking them would be worse: 'These drugs may not be perfect, but we must remember that when they were introduced they gave people an extra ten or twenty years when they would otherwise have died. In Africa, where the HIV epidermis has hit hardest and where more expensive medications are not an option, they are an absolute necessity', said Dr Brendan Payne, a co-author of the study.
The researchers will now look at how the damage believed to be caused by the drugs can be repaired. The study was published in Nature Genetics.
Copyright © 2011 BioNews
By Mehmet Fidanboylu
New research has revealed that a group of generic anti-HIV drugs may be linked to premature ageing. The study, which was carried out by UK scientists at the Institute of Genetic Medicine at Newcastle University, could explain why people treated with this class of drugs sometimes show signs of age-related conditions, such as heart disease and dementia.
The researchers studied muscle cells taken from people with HIV who had previously taken drugs known as nucleoside analogue reverse-transcriptase inhibitors (NRTIs) and found that DNA in the mitochondria of their cells had accumulated a number of errors that was more comparable to healthy people 20 or 30 years older.
'The DNA in our mitochondria gets copied throughout our lifetimes and, as we age, naturally accumulates errors. We believe that these drugs accelerate the rate at which these errors build up', said Professor Patrick Chennery, who led the study, adding: 'Over the space of, say, ten years, a person's mitochondrial DNA may have accumulated the same amount of errors as a person who has natural aged twenty or thirty years'.
NRTIs were a major breakthrough in the battle against HIV when they were developed in the late 1980s. But side-effects such as premature ageing and frailty have meant that they have been replaced by a cocktail of more recent drugs. However, NRTIs are generally favoured over these new drugs in developing countries due to their lower costs.
Until now it has not been clear why NRTIs, which include AZT or zidovudine, have these side-effects. 'HIV clinics were seeing patients who had otherwise been successfully treated but who showed signs of being much older than their years. This was a real mystery', said Professor Chinnery, 'but colleagues recognised many similarities with patients affected by mitochondrial diseases... and referred them to our clinic'.
Defects in mitochondrial DNA are often seen in age-related conditions, although it is not yet known whether this is a cause or consequence of taking the drugs.
It was estimated in 2009 that 33.3 million people had HIV, and of these 22.5 million live in Africa. The researchers were keen to stress that while NRTIs do sometimes have side-effects, not taking them would be worse: 'These drugs may not be perfect, but we must remember that when they were introduced they gave people an extra ten or twenty years when they would otherwise have died. In Africa, where the HIV epidermis has hit hardest and where more expensive medications are not an option, they are an absolute necessity', said Dr Brendan Payne, a co-author of the study.
The researchers will now look at how the damage believed to be caused by the drugs can be repaired. The study was published in Nature Genetics.
Copyright © 2011 BioNews
Maraviroc Switch Collaborative Study (MARCH)
MARCH is an international, multicentre trial planning to enroll 560 HIV-1 infected patients who are currently on 2N(t)RTI + PI/r regimen and virologically suppressed.
Participants will be randomized (1:2:2) to one of three treatment groups: to continue their current treatment regimen, maraviroc dose at 150 mg twice daily with PI/r, or maraviroc at 300 mg twice daily with 2N(t)RTI. As the participants population have HIV RNA <200 copies/mL, the phenotypic assessment of tropism cannot be used to determine tropism, instead we will employ the genotypic assessment of tropism by sequencing the V3 loop of the HIV envelope.
The main aim of this study is to investigate whether switching to maraviroc, in combination with either RTI or PI/r, is as good at keeping the HIV viral load undetectable as the combination of RTI with PI/r. The other aim is to see if switching to these combinations with maraviroc will improve some of the side effects that can be seen when people take combination therapy including RTI and PI/r.
The study hypothesis is that in stable, virologically suppressed (plasma HIV-RNA <200 copies/mL) patients with no history of prior virological failure, a switch to either MVC dosed at 300mg twice daily (bid) combined with the same 2N(t)RTI backbone regimen or MVC dosed at 150mg twice daily (bid) with the current PI/r (or 300mg bid at the discretion of the investigator if the PI/r is fosamprenavir/r) provides similar (non-inferior) antiretroviral efficacy compared to continuation of the current 2N(t)RTI + PI/r regimen.
Copyright © 2011 ClinicalTrials.gov
MARCH is an international, multicentre trial planning to enroll 560 HIV-1 infected patients who are currently on 2N(t)RTI + PI/r regimen and virologically suppressed.
Participants will be randomized (1:2:2) to one of three treatment groups: to continue their current treatment regimen, maraviroc dose at 150 mg twice daily with PI/r, or maraviroc at 300 mg twice daily with 2N(t)RTI. As the participants population have HIV RNA <200 copies/mL, the phenotypic assessment of tropism cannot be used to determine tropism, instead we will employ the genotypic assessment of tropism by sequencing the V3 loop of the HIV envelope.
The main aim of this study is to investigate whether switching to maraviroc, in combination with either RTI or PI/r, is as good at keeping the HIV viral load undetectable as the combination of RTI with PI/r. The other aim is to see if switching to these combinations with maraviroc will improve some of the side effects that can be seen when people take combination therapy including RTI and PI/r.
The study hypothesis is that in stable, virologically suppressed (plasma HIV-RNA <200 copies/mL) patients with no history of prior virological failure, a switch to either MVC dosed at 300mg twice daily (bid) combined with the same 2N(t)RTI backbone regimen or MVC dosed at 150mg twice daily (bid) with the current PI/r (or 300mg bid at the discretion of the investigator if the PI/r is fosamprenavir/r) provides similar (non-inferior) antiretroviral efficacy compared to continuation of the current 2N(t)RTI + PI/r regimen.
Copyright © 2011 ClinicalTrials.gov
Sunday, July 03, 2011
Study Reveals Why Some HIV-Infected People can Handle the Disease Better Than Others
The mechanism of how the immune system of the infected people handles HIV, and how HIV evades the immune system’s response has been revealed in a new study.
Researchers at Case Western Reserve University School of Medicine have discovered a long-sought cellular factor that works to inhibit HIV infection of myeloid cells.
Myeloid cells are a subset of white blood cells that display antigens and hence are important for the body’s immune response against viruses and other pathogens.
The factor, a protein called SAMHD1, is part of the nucleic acid sensing machinery within the body’s own immune system. It keeps cells from activating immune responses to the cells own nucleic acids, thus preventing certain forms of autoimmunity from developing.
SAMHD1 factor, researchers have found, can also sense and interfere with infection of myeloid cells, such as macrophages and dendritic cells, with HIV-1 and related immunodeficiency viruses.
As such, SAMHD1 prevents the synthesis of virus copies in these cells, according to research led by Jacek Skowronski, PhD, a professor in the Department of Molecular Biology and Microbiology.
“The identification of SAMHD1 and its function may help to explain why some infected individuals can control HIV infection better than others,” Dr. Skowronski said.
“Ultimately, it could also provide a basis for conceiving of new therapies and treatment approaches to block HIV infection and/or its replication in infected individuals, and to stimulate body’s own immune response to HIV,” he added.
The study was recently published in the journal Nature.
Copyright © 2011 MeD India
The mechanism of how the immune system of the infected people handles HIV, and how HIV evades the immune system’s response has been revealed in a new study.
Researchers at Case Western Reserve University School of Medicine have discovered a long-sought cellular factor that works to inhibit HIV infection of myeloid cells.
Myeloid cells are a subset of white blood cells that display antigens and hence are important for the body’s immune response against viruses and other pathogens.
The factor, a protein called SAMHD1, is part of the nucleic acid sensing machinery within the body’s own immune system. It keeps cells from activating immune responses to the cells own nucleic acids, thus preventing certain forms of autoimmunity from developing.
SAMHD1 factor, researchers have found, can also sense and interfere with infection of myeloid cells, such as macrophages and dendritic cells, with HIV-1 and related immunodeficiency viruses.
As such, SAMHD1 prevents the synthesis of virus copies in these cells, according to research led by Jacek Skowronski, PhD, a professor in the Department of Molecular Biology and Microbiology.
“The identification of SAMHD1 and its function may help to explain why some infected individuals can control HIV infection better than others,” Dr. Skowronski said.
“Ultimately, it could also provide a basis for conceiving of new therapies and treatment approaches to block HIV infection and/or its replication in infected individuals, and to stimulate body’s own immune response to HIV,” he added.
The study was recently published in the journal Nature.
Copyright © 2011 MeD India
Why people with HIV suffer memory loss despite potent therapy
Researchers at Albert Einstein College of Medicine of Yeshiva University have solved a longstanding medical mystery – why so many people with HIV experience memory loss and other cognitive problems despite potent antiretroviral therapy.
Even though antiretroviral treatment suppresses HIV replication and slows the progress of HIV disease, between 40 and 60 percent of HIV-infected people eventually develop mild-to-moderate neurological deficits, and up to 5 percent develop full-blown dementia.
Until now, researchers have not been able to explain why these complications, collectively known as neuroAIDS, occur.
In a previous study, the Einstein researchers found that HIV infects about 5 percent of brain cells known as astrocytes.
These cells bolster the blood-brain barrier, a network of blood vessels that prevents harmful substances from crossing into the brain from the bloodstream.
Now, they have shown that even this low-level of astrocyte infection can profoundly damage the blood-brain barrier.
“The relatively few infected astrocytes emit toxic signals through specialized channels that kill neighboring uninfected astrocytes, ultimately weakening the blood-brain barrier and allowing harmful compounds to enter the brain,” said senior author Joan Berman, Ph.D., professor of pathology and of microbiology and immunology at Einstein.
The evidence came from a laboratory model of the blood-brain barrier constructed of human cells and from examining brain tissue of macaque monkeys infected with the simian form of HIV.
The results suggest that drugs capable of reducing the damaging signaling cascades triggered by HIV-infected astrocytes might help in preventing or treating neuroAIDS.
Their findings were published in the June 29 issue of The Journal of Neuroscience. (ANI)
Copyright © 2011 Truth Dive
Researchers at Albert Einstein College of Medicine of Yeshiva University have solved a longstanding medical mystery – why so many people with HIV experience memory loss and other cognitive problems despite potent antiretroviral therapy.
Even though antiretroviral treatment suppresses HIV replication and slows the progress of HIV disease, between 40 and 60 percent of HIV-infected people eventually develop mild-to-moderate neurological deficits, and up to 5 percent develop full-blown dementia.
Until now, researchers have not been able to explain why these complications, collectively known as neuroAIDS, occur.
In a previous study, the Einstein researchers found that HIV infects about 5 percent of brain cells known as astrocytes.
These cells bolster the blood-brain barrier, a network of blood vessels that prevents harmful substances from crossing into the brain from the bloodstream.
Now, they have shown that even this low-level of astrocyte infection can profoundly damage the blood-brain barrier.
“The relatively few infected astrocytes emit toxic signals through specialized channels that kill neighboring uninfected astrocytes, ultimately weakening the blood-brain barrier and allowing harmful compounds to enter the brain,” said senior author Joan Berman, Ph.D., professor of pathology and of microbiology and immunology at Einstein.
The evidence came from a laboratory model of the blood-brain barrier constructed of human cells and from examining brain tissue of macaque monkeys infected with the simian form of HIV.
The results suggest that drugs capable of reducing the damaging signaling cascades triggered by HIV-infected astrocytes might help in preventing or treating neuroAIDS.
Their findings were published in the June 29 issue of The Journal of Neuroscience. (ANI)
Copyright © 2011 Truth Dive
Saturday, July 02, 2011
Who Should Consider HIV Tropism Testing for Maraviroc Response?
Experts, such as the U.S. Food and Drug Administration and the Department of Health and Human Services, agree that all people planning to start maraviroc (Selzentry®) therapy should have human immunodeficiency virus may also be considered for people taking maraviroc who are not responding as hoped.
Before starting therapy
Maraviroc drug information (approved by the US Food and Drug Administration) says that only adults with CCR5-tropic HIV should take maraviroc. Maraviroc only works in people with CCR5-tropic HIV. It does not work on those with CXCR4-tropic HIV, or HIV that uses both receptors.
The way to find out which receptor your kind of HIV infection uses is with HIV tropism testing. Everyone considering maraviroc therapy needs to have HIV tropism testing before taking the drug. In rare cases, therapy may start before these test results are available. In these rare cases, testing should be done as soon as possible.
When therapy doesn’t work
Some experts believe that HIV tropism testing should be repeated if maraviroc doesn’t work as expected. There are many reasons maraviroc may not work, including a dose that is too low, not taking the drug regularly enough, or being resistant to the drug for reasons other than HIV tropism.
Another important reason maraviroc may stop working is that HIV viral tropism can change over time. Someone who has CCR5-tropic virus at the beginning of therapy can later have CXCR4-tropic virus.
A Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents recommends:
“Coreceptor tropism assay should be performed whenever the use of a CCR5 inhibitor is being considered.”
“Coreceptor tropism testing might also be considered for patients who exhibit virologic failure on a CCR5 inhibitor.”
Copyright © 2011 Aspirus Genetics
Experts, such as the U.S. Food and Drug Administration and the Department of Health and Human Services, agree that all people planning to start maraviroc (Selzentry®) therapy should have human immunodeficiency virus may also be considered for people taking maraviroc who are not responding as hoped.
Before starting therapy
Maraviroc drug information (approved by the US Food and Drug Administration) says that only adults with CCR5-tropic HIV should take maraviroc. Maraviroc only works in people with CCR5-tropic HIV. It does not work on those with CXCR4-tropic HIV, or HIV that uses both receptors.
The way to find out which receptor your kind of HIV infection uses is with HIV tropism testing. Everyone considering maraviroc therapy needs to have HIV tropism testing before taking the drug. In rare cases, therapy may start before these test results are available. In these rare cases, testing should be done as soon as possible.
When therapy doesn’t work
Some experts believe that HIV tropism testing should be repeated if maraviroc doesn’t work as expected. There are many reasons maraviroc may not work, including a dose that is too low, not taking the drug regularly enough, or being resistant to the drug for reasons other than HIV tropism.
Another important reason maraviroc may stop working is that HIV viral tropism can change over time. Someone who has CCR5-tropic virus at the beginning of therapy can later have CXCR4-tropic virus.
A Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents recommends:
“Coreceptor tropism assay should be performed whenever the use of a CCR5 inhibitor is being considered.”
“Coreceptor tropism testing might also be considered for patients who exhibit virologic failure on a CCR5 inhibitor.”
Copyright © 2011 Aspirus Genetics
Thursday, June 30, 2011
HIV disrupts blood-brain barrier
HIV weakens the blood-brain barrier — a network of blood vessels that keeps potentially harmful chemicals and toxins out of the brain — by overtaking a small group of supporting brain cells, according to a new study in the June 29 issue of The Journal of Neuroscience. The findings may help explain why some people living with HIV experience neurological complications, despite the benefits of modern drug regimens that keep them living longer.
Standard antiretroviral treatments successfully suppress the replication of HIV and slow the progression of the disease. Yet recent studies show 40 to 60 percent of patients on such therapy continue to experience mild to moderate neurological deficits — including memory loss and learning challenges.
In the new study, Eliseo Eugenin, PhD, of Albert Einstein College of Medicine, found that HIV infection in a small number of supporting brain cells called astrocytes breaks down the blood-brain barrier, despite low to undetectable viral production. Under normal conditions astrocytes help bolster the blood vessels comprising the barrier.
To test if HIV interfered with this support system, Eugenin and his colleagues built a model of the blood-brain barrier using human cells in the laboratory. In a previous study, the researchers found HIV infects around 5 percent of astrocytes. In the current study, the researchers found the presence of HIV in a similar percentage of astrocytes led to the death of nearby uninfected cells and made the barrier more permeable.
As the neighboring cells died, however, HIV-infected astrocytes survived. Astrocytes exchange chemical signals through specialized molecules called gap junctions. When they were blocked in the model, it prevented the changes to the blood-brain barrier and nearby cells, suggesting the infected astrocytes relay toxic signals to neighboring cells through the gap junctions.
“Our results suggest HIV infection of astrocytes may be important in the onset of cognitive impairment in people living with the disease,” Eugenin said. “New therapies are needed that not only target the virus, but also to stop the virus from spreading damage to other uninfected brain cells.”
Eugenin’s group also analyzed the brain tissue of macaque monkeys infected with the simian form of HIV. Similar to what they saw in the human blood-brain barrier model, the researchers found uninfected cells in contact with HIV-infected astrocytes died, while infected astrocytes remained alive as the disease progressed.
“Researchers have been stymied to explain why HIV-associated neurological complications persist, despite potent combination antiviral therapies that have dramatically improved health and survival,” said Igor Grant, an expert who studies HIV-associated neurocognitive impairment at the University of California, San Diego. “This study provides a possible explanation indicating that minute numbers of infected astrocytes can trigger a cascade of signals that could open the brain to various toxic influences.”
The findings open up the possibility of developing new therapeutic approaches that block or modify the transmission of signals from the HIV-infected astrocytes, added Grant, who was not affiliated with the study.
Copyright © 2011 Society for Neuroscience: http://www.sfn.org
HIV weakens the blood-brain barrier — a network of blood vessels that keeps potentially harmful chemicals and toxins out of the brain — by overtaking a small group of supporting brain cells, according to a new study in the June 29 issue of The Journal of Neuroscience. The findings may help explain why some people living with HIV experience neurological complications, despite the benefits of modern drug regimens that keep them living longer.
Standard antiretroviral treatments successfully suppress the replication of HIV and slow the progression of the disease. Yet recent studies show 40 to 60 percent of patients on such therapy continue to experience mild to moderate neurological deficits — including memory loss and learning challenges.
In the new study, Eliseo Eugenin, PhD, of Albert Einstein College of Medicine, found that HIV infection in a small number of supporting brain cells called astrocytes breaks down the blood-brain barrier, despite low to undetectable viral production. Under normal conditions astrocytes help bolster the blood vessels comprising the barrier.
 |
| Astrocytes (pictured in green) help to support blood vessels (red) that act as the blood-brain barrier - a network that keeps potentially harmful chemicals and toxins out of the brain. This image shows the close interaction between the cells in the human brain. Credit: Eugenin, et al. The Journal of Neuroscience 2011. |
As the neighboring cells died, however, HIV-infected astrocytes survived. Astrocytes exchange chemical signals through specialized molecules called gap junctions. When they were blocked in the model, it prevented the changes to the blood-brain barrier and nearby cells, suggesting the infected astrocytes relay toxic signals to neighboring cells through the gap junctions.
“Our results suggest HIV infection of astrocytes may be important in the onset of cognitive impairment in people living with the disease,” Eugenin said. “New therapies are needed that not only target the virus, but also to stop the virus from spreading damage to other uninfected brain cells.”
Eugenin’s group also analyzed the brain tissue of macaque monkeys infected with the simian form of HIV. Similar to what they saw in the human blood-brain barrier model, the researchers found uninfected cells in contact with HIV-infected astrocytes died, while infected astrocytes remained alive as the disease progressed.
“Researchers have been stymied to explain why HIV-associated neurological complications persist, despite potent combination antiviral therapies that have dramatically improved health and survival,” said Igor Grant, an expert who studies HIV-associated neurocognitive impairment at the University of California, San Diego. “This study provides a possible explanation indicating that minute numbers of infected astrocytes can trigger a cascade of signals that could open the brain to various toxic influences.”
The findings open up the possibility of developing new therapeutic approaches that block or modify the transmission of signals from the HIV-infected astrocytes, added Grant, who was not affiliated with the study.
Copyright © 2011 Society for Neuroscience: http://www.sfn.org
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