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People With Subtype A or C May Respond More Rapidly to HAART
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6th European HIV Drug Resistance Workshop
March 26-28, 2008
Budapest, Hungary
Mark Mascolini
UK residents infected with HIV-1 subtype A or C apparently responded to their first highly active antiretroviral therapy (HAART) regimen faster than people with subtype B, the dominant viral family in Western Europe and North America [1]. CD4 gains and treatment changes did not vary significantly from one subtype to the next.
This 2116-person study included 73% with subtype B, 13% with C, 3% with A, 3% with CRF_AG, 2% with D, and 6% with other subtypes or circulating recombinant forms. All cohort members were older than 16, and none had antiretroviral experience when they began HAART. Two thirds took a nonnucleoside-based regimen and one quarter took a ritonavir-boosted or -unboosted protease inhibitor. Two thirds of the study group began HAART in 2001 or later. While 69% of these people were white, 18% were black African. About two thirds were men who have sex with men, 16% heterosexual women, and 10% heterosexual men.
As expected, race and risk group strongly correlated with HIV-1 subtype (P < 0.001). Subtype B-infected people were older and had both higher CD4 counts and higher viral loads than people with other subtypes (P < 0.001). The subtype B group took efavirenz significantly more often than others.
After 12 months of treatment, equivalent proportions infected with each subtype had a viral load below 50 copies, ranging from 89% of people with subtype B to 94% with subtype C and 97% with subtype A. Defining rebound as consecutive viral loads above 1000 copies or one load above 1000 and a major regimen change, the investigators also found equivalent rebound rates across subtypes, including 17% with subtype B, 20% with subtype C, and 20% with subtype A.
Time to first viral load measurement measured about 1 month for each subtype, but median time to viral suppression was swifter with subtype A (2.6 months) and C (2.8 months) than with subtype C (3.1 months). Multivariate analysis adjusting for age, treatment center, type of regimen, calendar year of starting HAART, and baseline CD4 count and viral load found that subtype A-infected people had a 35% better chance of faster suppression than people with subtype B (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.04 to 1.74, P = 0.02). Subtype C-infected people had a 16% better chance of faster suppression than the subtype B group (HR 1.16, 95% CI 1.01 to 1.33, P = 0.04).
Time between viral load measurements stood at about 2.6 months regardless of subtype. Yet multivariate analysis adjusting for the same variables plus time to suppression discerned a 40% chance of faster rebound with subtype C than with subtype B (HR 1.40, 95% CI 1.00 to 1.95, P = 0.05). But when statisticians eliminated rebounds due to poor adherence or stopping therapy altogether, time to rebound no longer differed between these two groups.
Subtype had no impact on CD4 gains with therapy. Although people with subtype B started antiretrovirals with more CD4 cells, people with subtype A or C had parallel CD4 gains through 36 months of follow-up.
Viral load assays are more sensitive for subtype B virus than for other subtypes. As a result actual viral loads may have been even lower in people infected with subtype A or C than the loads recorded, and lower loads take less time to become undetectable. Chris Petropoulos of Monogram Biosciences suggested such discrepancies may contribute to the apparently faster viral suppression in people with subtype A or C, even though the multivariate analysis controlled for pretreatment load.
Reference
1. Geretti AM, Harrison L, Green H, Dunn D. Exploring the effect of HIV-1 subtype on virological and immunological responses to first-line HAART. 6th European HIV Drug Resistance Workshop. March 26-28, 2008. Budapest. Abstract 30.
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