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Chances of Virologic Response Halved in Blacks vs Nonblacks in ART Trials
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XIX International AIDS Conference, July 22-27, 2012, Washington, DC
Mark Mascolini
African Americans in recent randomized antiretroviral therapy (ART) trials had a virologic success rate half that of nonblacks, according to results of a 6-study meta-analysis [1]. In five of the six studies, black race independently conferred a response disadvantage, and the sixth study showed a strong trend in that direction.
Blacks accounted for 44% of newly recorded HIV infections in the United States in 2009, but they made up only 14% of the US population. African Americans are consistently underrepresented in antiretroviral trials, but many such trials record some evidence of a worse virologic response rate by blacks than by other racial groups.
To get a better perspective on antiretroviral response among blacks in antiretroviral trials, a collaboration of US academic and industry researchers planned this meta-analysis. They searched for antiretroviral trials published or presented between January 1996 and December 2011 that enrolled antiretroviral-naive participants and reported virologic success and failure by race.
Six of the 12 studies had a similar design, including a 96-week time-to-loss-of-virologic-response (TLOVR) endpoint of a viral load below 50 copies, so the researchers considered those trials for meta-analysis. The six studies were Gilead Sciences studies 903 and 934, ECHO and THRIVE (pooled), ARTEMIS, and HEAT. Key antiretrovirals analyzed in these trials were darunavir/ritonavir, lopinavir/ritonavir, rilpivirine, and efavirenz--usually with tenofovir/emtricitabine or abacavir/lamivudine.
Calculating hazard ratios (HR) of virologic success (under 50 copies) in a 96-week TLOVR analysis, the investigators found a substantially lower chance of success (usually a significantly lower chance) among black trials participants:
-- GS 903: HR 0.43 (95% confidence interval [CI] 0.29 to 0.66)
-- GS 934: HR 0.63 (95% CI 0.41 to 0.96)
-- ECHO/THRIVE: HR 0.50 (95% CI 0.38 to 0.67)
-- ARTEMIS: HR 0.58 (95% CI 0.33 to 1.03, not significant)
-- HEAT: HR 0.53 (95% CI 0.39 to 0.73)
-- Overall: HR 0.52 (95% CI 0.44 to 0.62)
The overall analysis indicated that blacks has a 48% lower chance of a 96-week sub-50-copy response than nonblacks, a highly significant difference (P < 0.0001).
Other trials assessed were ACTG 5095 (efavirenz versus Trizivir), ACTG 5142 (efavirenz versus lopinavir), ACTG 5202 (efavirenz or atazanavir with different nucleoside backbones), KLEAN (fosamprenavir versus lopinavir), and GRACE (darunavir plus an optimized background regimen). All of these trials yielded some evidence of a worse virologic response among blacks.
One shortcoming of many of these trials, the researchers observed, is lack of adherence data by race. Other potentially relevant variables that remained unanalyzed were mental health, cost, health literacy, and food security. Other factors that may play a role in the diminished response among blacks, the researched proposed, include difference in pharmacokinetics and psychosocial barriers.
They cautioned that "a hypothesis that black participants across every arm of randomized controlled trials for the past decade have been unable to adhere to regimens as the primary explanation for this racial disparity should be of concern to investigators and the community."
Reference
1. Spencer DE, Walker IL, Evans C, et al. A meta-analysis of the differences in ART virologic failure rates in randomized clinical trials: do blacks consistently have lower ART efficacy and poor treatment outcomes? XIX International AIDS Conference. July 22-27, 2012. Washington, DC. Abstract THPE037.
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