Tuesday, May 31, 2011

Can Cannabis Reduce HIV Disease Progression? 
By Liz Highleyman

Cannabis has been shown in studies to improve appetite, relieve chronic pain, and reduce nausea due to chemotherapy. Many people with HIV/AIDS use medical marijuana to combat wasting and other symptoms, which raises questions about what effects it might have on HIV and its progression.

Many immune cells express cannabinoid receptors, indicating that cannabis may influence immune function. Some prior research suggested that marijuana use is associated with HIV disease progression, but such studies were prone to confounding by socioeconomic and other factors related to illegal drug use.

As described in the June 2011, issue of AIDS Research and Human Retroviruses, Patricia Molina and colleagues from Louisiana State University Health Sciences Center examined the impact of ongoing administration of delta-9-tetrahydrocannabinol (THC) in macaque monkeys exposed to simian immunodeficiency virus (SIV).

Eight rhesus macaques received twice-daily intramuscular injections of either THC or a placebo. After 28 days, they were intravenously inoculated with a highly infectious dose of SIV. The researchers looked and immune and metabolic indicators of disease progression during the initial 6-month asymptomatic phase after infection.

THC administration did not significantly increase viral load or exacerbate immune dysfunction.

After exposure to SIV, the monkeys showed measurable viral loads, decreased CD4/CD8 T-cell ratios, and increased CD8 cell proliferation.

Administration of cannabis prior to infection produced little or no effects on these parameters.

THC-treated monkeys lost CD4 cells more slowly than the placebo group.

Monkeys given THC had a significantly lower early mortality rate compared with placebo-treated animals.

THC-treated monkeys had lower plasma and cerebrospinal fluid SIV viral load than those in the placebo group.

Monkeys in the THC group also experienced less wasting, though the difference did not reach statistical significance.

In a laboratory study, THC decreased SIV replication in MT4-R5?cells in vitro.
“These results indicate that chronic [THC] does not increase viral load or aggravate morbidity and may actually ameliorate SIV disease progression,” the study authors concluded.

“Two of the [placebo-treated] animals succumbed to SIV infection shortly after 5 months, and a third reached end stage at 7 months,” they elaborated in their discussion. “Among the [THC-treated] animals, the first animal did not reach end stage until 11 months post-SIV inoculation. “

“We speculate that reduced levels of SIV, retention of body mass, and attenuation of inflammation are likely mechanisms for [THC]-mediated modulation of disease progression that warrant further study,” they wrote.

Investigator affiliations: Departments of Physiology, Pharmacology, Medicine, Microbiology, and Pathology, Louisiana State University Health Sciences Center, New Orleans, LA; and School of Public Health, Alcohol Research Center, and Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA.

PE Molina, P Winsauer, P Zhang, et al. Cannabinoid Administration Attenuates the Progression of Simian Immunodeficiency Virus. AIDS Research and Human Retroviruses 27(6): 585-592 (free full text). June 2011


Saturday, May 28, 2011

HIV viral load detectable after just 2 days without meds
By Fran Lowry

There is a dose–response relation between days of missed HIV medications and the subsequent viral load.

The total amount of nonadherent time with HIV antiretroviral therapy over the course of a month affects the risk of having a detectable viral load starting at 14 days, but an interruption of just 2 days will cause the viral load to rise, according to research presented here at the 6th International Conference on HIV Treatment and Prevention Adherence, sponsored by the International Association of Physicians in AIDS Care (IAPAC).

The findings, from an analysis of the MACH-14 study, were presented by Becky L. Genberg, PhD, MPH, from Brown University, Providence, Rhode Island.

There is a dose–response relation between days of missed HIV medications and the subsequent viral load. Moreover, it appears that consecutive days of missed medications of approximately 2 weeks are the most damaging to patient health, compared with shorter interruptions or overall medication-free days, Dr. Genberg said.

“When patients stop taking their medication, their viral load starts to go up almost immediately,” she told Medscape Medical News.

The MACH-14 study combines data from 16 studies at 14 sites in the United States. In this analysis, Dr. Genberg and her team focused on 768 individuals with 2399 viral load measures, and looked at patterns of nonadherence in the 28 days prior to measuring the viral load.

The study sample was 73% male, 42% African American, 34% white, and 17% Hispanic/Latino. The median age was 40 years (interquartile range [IQR], 35 to 46), and 31% were treatment-naïve at baseline. The median viral load was 400 copies/mL (IQR, 400 to 1454).

After adjustment for sociodemographics, total nonadherent days, and time since longest interruption, a dose–response relation between the length of the longest treatment interruption and increased viral load was observed.

The study found that viral load began to increase in as little as 48 hours after discontinuing HIV medication.

After 2 to 6 days, the viral load increased 25%. Between 14 and 20 days, viral load continued to increase significantly (P < .001), and participants whose treatment interruption lasted 3 weeks or longer saw their viral load increase 3-fold, Dr. Genberg said.

“The patterns of adherence seem to matter. We would like a more careful consideration, looking at nonadherence and the different patterns of nonadherence,” she said in an interview. “We would also like to focus on understanding ways to prevent and to intervene to prevent these consecutive treatment interruptions to maximize the effectiveness of treatment.”

“The capacity to pool large datasets is vital to answer questions regarding the impact of different patterns of nonadherence on HIV treatment outcomes,” said conference cochair Christopher M. Gordon, PhD, chief of the Secondary HIV Prevention and Translational Research Branch and associate director for prevention at the National Institute of Mental Health in Bethesda, Maryland.

“These findings have important implications for adherence interventions in both domestic and international settings,” he told Medscape Medical News. “Providers could make more concerted efforts to reduce longer episodes of nonadherence, and in settings where drug stock-outs or other socioeconomic barriers make treatment interruptions more likely, systemic or structural interventions may be needed to prevent these gaps in treatment.”

Jose M. Zuniga, PhD, president of IAPAC and conference cochair, noted that the results of the study “speak directly to a growing call from clinicians, as well as patients, for more sophisticated discussions about the importance of maintaining optimal adherence to antiretroviral therapy.”

He told Medscape Medical News: “ ‘Because I said so’, and ‘because you should’ are no longer strong enough reasons for patients to observe proper medication-taking behaviors.”

Dr. Zuniga added that tools are needed to help clinicians deal with a variety of adherence-related challenges. These include polypharmacy challenges “posed by an aging population of patients on antiretroviral therapy who are taking myriad other drugs, including for comorbid conditions such as cardiovascular disease and/or viral hepatitis.”

This study was supported by the National Institute of Mental Health and the Agency for Healthcare Research and Quality. Dr. Genberg, Dr. Gordon, and Dr. Zuniga have disclosed no relevant financial relationships.

Presented May 23, 2011. 6th International Conference on HIV Treatment and Prevention Adherence: Abstract 70087.

European Aids Treatment Group