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Antiretroviral Therapy Is Effective against Multiple HIV-1 Subtypes

Antiretroviral therapy (ART) works well regardless of HIV subtype, according to a report by investigators with the U.K. Collaborative HIV Cohort Study, published in the May 1, 2009 issue of Clinical Infectious Diseases.

It has been proposed that subtype-related variability of HIV-1 may influence virological and immunological response to combination ART, the authors noted as background. But studies to date have mainly looked at treatment outcomes in people with subtype B, the predominant form in the U.S. and Europe, where most clinical trials of antiretroviral drugs have been conducted. HIV-1 subtypes A, C, D, and recombinant forms are predominant in Africa and Asia.

The researchers used data from the linked U.K. Collaborative HIV Cohort Study and U.K. Collaborative Group on HIV Drug Resistance databases to compare treatment response in more than 2000 antiretroviral-naive patients infected with HIV subtype B (n=1550; 73%), subtype C (n=272; 13%), subtype A (n=66; 3%), circulating recombinant form (CRF) AG (n=57; 3%), or subtype D (n=41; 2%); the remainder had various minor strains or type could not be determined (n = 130; 6% combined).

Patients with subtype B were predominantly gay white men, while non-B patients were more likely to be female and black. Before starting treatment, average HIV viral loads and CD4 counts were similar in subtype B and non-B patients. While ART regimens were similar overall, there were some differences (e.g., non-B patients were less likely to receive efavirenz (Sustiva) because it is contraindicated during pregnancy).

Over a median period of 39 months, the investigators looked at time to reach undetectable viral load (< 50 copies/mL), time to virological rebound (HIV RNA >1000 copies/mL), and CD4 cell increases.

Results

• Overall, 90% of all patients achieved undetectable viral load within 12 months after starting combination ART, and the rates were similar across subtypes:

Subtype B: 89%;
Subtype C: 94%;
Subtype A: 97%.

• 335 participants (18%) subsequently experienced virological rebound.
• In adjusted analyses, viral load suppression occurred more rapidly in patients infected with subtype C (hazard ratio [HR] 1.16; P = 0.04) and subtype A (HR 1.35; P = 0.02) relative to subtype B.
• Virological rebound was marginally more common and occurred slightly more rapidly in patients with subtype C compared with subtype B (HR 1.40; P = 0.05).
• In a multivariate analysis controlling for potential confounding factors (including adherence and race/ethnicity), however, these differences were no longer statistically significant.
• Although patients with subtype B infection had higher baseline CD4 counts and maintained this advantage after starting therapy, CD4 cell gains were comparable, and recovery occurred at similar rates in people with all subtypes.

Based on these findings, the authors concluded, "Patients infected with prevalent non-B subtypes were as likely to achieve viral load suppression as persons infected with subtype B and showed comparable rates of CD4 cell count recovery. HAART achieves excellent outcomes regardless of the infecting subtype."

In an accompanying editorial, Sergei Kosakovsky Pond and Davey Smith from the University of California at San Diego and Veterans Affairs San Diego Healthcare System wrote, "Modern antiretroviral therapy works well in the handful of non-B subtypes studied so far and will certainly save lives, independent of the subtype of the infecting virus," but added that more research in non-B populations is needed.

Royal Free Hampstead NHS Trust, Departments of Virology and Primary Care and Population Sciences, University College London Medical School; Medical Research Council Clinical Trial Unit; Specialist and Reference Microbiology Division, Health Protection Agency, London, UK.

5/22/09

Reference

AM Geretti, L Harrison, H Green, and other (UK Collaborative Group on HIV Drug Resistance. Effect of HIV-1 subtype on virologic and immunologic response to starting highly active antiretroviral therapy. Clinical Infectious Diseases 48(9): 1296-1305. May 1, 2009. (Abstract).

SL Kosakovsky Pond and DM Smith. Are all subtypes created equal? The effectiveness of antiretroviral therapy against non-subtype B HIV-1. Clinical Infectious Diseases 48(9): 1306-1309. May 1, 2009.