Older HIV+ People May Benefit from Earlier ART 
By Liz Highleyman

SUMMARY
Starting antiretroviral treatment at higher CD4 T-cell counts predicted better long-term immune recovery in a large U.S. cohort, while age over 50 years and hepatitis B or C coinfection were linked to smaller CD4 cell gains.

Combination highly active antiretroviral therapy (HAART) typically leads to viral suppression and recovery of CD4 T-cells, but outcomes can vary from person to person.

As described in the May 20, 2011, advance online edition of the Journal of Acquired Immune Deficiency Syndromes, Li Xiuhong from Johns Hopkins Bloomberg School of Public Health and colleagues looked at predictors of CD4 cell counts and HIV viral load among people on long-term HAART.

The analysis included 614 men in the long-running Multicenter AIDS Cohort Study (MACS), an observational trial that has followed gay and bisexual men with HIV/AIDS in 4 U.S. cities since 1984. The group included in this analysis had been taking combination therapy for 5 to 12 years.

Nearly half (47%) were younger than 40 years when they started HAART and 12% were older than 50. About half (53%) used protease inhibitor regimens (70% of them boosted with ritonavir), while 42% used non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 5% used triple nucleoside/nucleoside reverse transcriptase inhibitor (NRTI) combinations.

Results

At 5-12 years after starting HAART, the overall median CD4 T-cell count was 586 cells/mm3. A majority of participants had more than 500 cells/mm3, the current threshold for HAART initiation. 78% of HIV RNA measurements showed undetectable viral load. Predictors of higher CD4 counts after 5-12 years on HAART included:

Higher CD4 T-cell count before starting HAART;

Higher total lymphocyte count (CD4 T-cells plus other immune cells) before HAART (> 1200 cells/mm3).

Larger CD4 T-cell gains during the first 5 years on HAART;

Good HIV viral load suppression during first 5 years on HAART;

Remaining on a stable first or second HAART regimen;

Good adherence;

Not having hepatitis B or C coinfection;

Age 50 years or older at HAART initiation.

CD4 cell gains tended to plateau after 5 years in people who started HAART with lower CD4 counts.

Older men experienced good CD4 cell recovery on average, with a mean adjusted CD4 count of 643 cells/mm3 after 10-12 years on HAART. However, among men who started therapy with 201-350 cells/mm3, the average was 578 cells/mm3 for those older than 50 compared with 670 cells/mm3 for those younger than 40 at HAART initiation.

Stated another way, the mean CD4 count of older men who started HAART with 351-500 cells/mm3 was similar to that of younger men who started with 201-350 cells/mm3 (643 vs 670 cells/mm3, respectively).

HIV RNA suppression during the first 5 years on HAART predicted subsequent viral suppression.
Based on these findings, the study authors concluded, “Immunological and virological responses in the first 5 years post-HAART predicted subsequent CD4 T-cell counts and HIV-1 RNA levels.”

“The association between age and subsequent CD4 T-cell count supports incorporating age in guidelines for use of HAART,” they added, suggesting that older people may benefit from starting treatment sooner, while their CD4 counts are still high.

Investigator affiliations: Departments of Epidemiology and Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; David Geffen School of Medicine at UCLA, Los Angeles, CA; Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Reference
L Xiuhong, JB Margolick, BD Jamieson, et al. CD4+ T-Cell Counts and Plasma HIV-1 RNA Levels Beyond 5 Years of Highly Active Antiretroviral Therapy (HAART). Journal of Acquired Immune Deficiency Syndromes (abstract). May 20, 2011 (Epub ahead of print).

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