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Black Race Tied to Virologic Failure in ACTG Trials--But Blacks Gained More CD4s
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18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
Black race independently raised the risk of first-line virologic failure in an analysis of five AIDS Clinical Trials Group (ACTG) studies [1]. The impact of race could not be explained by adherence or the sociodemographic variables considered. Yet blacks gained significantly more CD4 cells through 96 weeks of therapy than whites, even after statistical adjustment for pretreatment CD4 count.
Previous antiretroviral trials found a higher risk of virologic failure in African Americans than in whites. An often-proposed explanation of the higher failure rate in blacks involves sociodemographic factors such as poverty, worse access to health care, and obstacles to antiretroviral adherence. To test that explanation and to learn more about antiretroviral responses in blacks and white, ACTG investigators planned this study of antiretroviral-naive non-Hispanic black and white participants in five ACTG trials conducted from 1998 through 2005.
The analysis involved 2495 adults, including 1202 white men, 820 black men, 142 white women, and 331 black women. Median age across the trials stood at 37, median pretreatment CD4 count at 210, and median pretreatment viral load at 100,000 copies. The regimens tested included standard nonnucleoside and protease inhibitor combinations, a nucleoside-sparing combination of efavirenz and lopinavir/ritonavir, and four triple-class regimens. All but one study (A5073) had more than 96 weeks of follow-up.
The primary endpoint of the 5-study analysis was time to virologic failure, defined as time from study entry to the first of two consecutive viral loads above 1000 copies at or after week 16 and before week 24, or a confirmed viral load above 200 copies at or after week 24. In the initial calculation, blacks had a 60% higher risk of virologic failure than whites (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.4 to 1.9, P < 0.001). That result did not vary from regimen to regimen.
Further analysis adjusted for the potential impact of age, gender, disease status, comorbidities, mode of HIV transmission, depression, self-reported education level, alcohol use, belief in one's ability to take antiretrovirals regularly, perceived social support, and time-updated self-reported adherence. In this analysis, black race had a smaller impact on virologic response. But blacks still had a 40% higher risk of failure than whites, independently of other risk factors (HR 1.40, 95% CI 1.2 to 1.6, P < 0.001).
Three other factors also independently raised the risk of failure at the following hazard ratios (and 95% CIs):
-- Every 10-fold higher viral load (for failure at 0 to 6 months): HR 1.4 (1.2 to 1.7), P < 0.001
-- Hepatitis C virus positive: HR 1.4 (1.1 to 1.7), P = 0.005
-- Recent adherence below 100%: HR 2.6 (2.3 to 3.1), P < 0.001
Three factors marginally boosted the risk of virologic failure in this analysis: Every 10-fold higher pretreatment viral load raised the risk of failure at 6 to 12 months 10% (HR 1.1, 95% CI 1.0 to 1.2, P = 0.08). Not graduating from high school upped the failure risk 20% (HR 1.2, 95% CI 1.0 to 1.5, P = 0.07). And reporting little social support raised the risk 20% (HR 1.2, 95% CI 1.0 to 1.4, P = 0.11).
Every 50-cell higher pretreatment CD4 count lowered the risk of virologic failure (P = 0.022). And every 10 additional years of age made failure 20% less likely (HR 0.80, 95% CI 0.8 to 0.9, P < 0.001). Variables that did not affect virologic failure risk in this analysis were gender, hepatitis B positivity, and uncertainty that combination antiretrovirals have a positive effect.
Despite the greater risk of virologic failure among blacks, African Americans gained more CD4 cells through 96 weeks of treatment--though not through 24 or 48 weeks--in an intention-to-treat analysis (P = 0.05). That association held true after statistical adjustment for pretreatment variables including initial CD4 count: Through 96 weeks of treatment, blacks gained an average of 33 more CD4 cells than whites (95% CI 16 to 50). The ACTG investigators cautioned that this 33-cell gain may not be clinically meaningful.
Study limitations include a broad adherence measure (4-day recall) and lack of data on income, housing status, and access to health care. Although some of the regimens tested would not be considered standard of care, the investigators believe their findings are convincing because of the consistent impact of black race on virologic response across all combinations studied. The ACTG team has yet to analyze resistance data, which could offer further insights into adherence.
Reference
1. Ribaudo H, Smith K, Robbins G, et al. Race differences in the efficacy of initial ART on HIV infection in randomized trials undertaken by ACTG. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 50.
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