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Blacks and Women Have Worse Virologic Response
in Trial of ABC/3TC vs TDF/FTC
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5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
African Americans and women had worse week-96 virologic responses to a lopinavir/based regimen in the HEAT trial, regardless of whether they also took coformulated abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) [1]. In multivariate statistical analysis, African-American race independently predicted a worse virologic response but female gender did not.
The double-blind, placebo-matched HEAT trial randomized 688 antiretroviral-naive adults to once-daily ABC/3TC or TDF/FTC, both with 800/200 mg of lopinavir/ritonavir [2]. After 48 weeks a missing-equals-failure analysis (with switching allowed) determined that 68% randomized to ABC/3TC and 67% randomized to TDF/FTC had a viral load below 50 copies. After 96 weeks, sub-50-copy response rates were 60% with ABC/3TC and 58% with TDF/FTC. Responses were similar to both regimens when pretreatment viral load was above 100,000 copies or CD4 count under 50.
For the racial analysis, study participants declared their own race or ethnicity. Women tended to have lower pretreatment viral loads than men, and the same held true for African Americans compared with other racial/ethnic groups. An exception was the African-American group taking lopinavir/ritonavir plus ABC/3TC, which tended to have viral loads similar to those in other groups. Notably, HEAT had no formal assessment of adherence to therapy.
At week 96, regardless of treatment assignment, the HEAT team figured a substantially higher sub-50-copy response rate among Caucasians than African Americans, while Hispanics had an intermediate response rate:
· Caucasians on ABC/3TC 68% (97 of 143) or TDF/FTC 67% (99 of 147)
· Hispanics on ABC/3TC 58% (42 of 73) or TDF/FTC 58% (36 of 62)
· Blacks on ABC/3TC 50% (60 of 119) or TDF/FTC 48% (59 of 124)
Men also had better 96-week sub-50-copy response rates than women regardless of whether they took ABC/3TC or TDF/FTC:
· Men on ABC/3TC 62% (179 of 287) or TDF/FTC 59% (164 of 276)
· Women on ABC/3TC 46% (26 of 56) or TDF/FTC 52% (36 of 69)
Neither race nor gender appeared to affect CD4 gains in the two treatment arms. Women taking ABC/3TC had a greater median CD4 gain (+307) than women taking TDF/FTC (+262) and a greater median gain than men in both treatment groups (+245 with ABC/3TC or TDF/FTC). Despite the lower virologic response rate in women, few women had protocol-defined virologic failure in HEAT. The investigators did not calculate statistical significance of these racial or gender differences.
Multivariate statistical analysis that considered gender, race, and other variables determined that African-American race independently raised the risk of failure, whereas female gender did not. The investigators did not present details of this analysis.
The impaired virologic responses among African Americans and women in HEAT reflect similar findings in the KLEAN trial of fosamprenavir/ritonavir versus lopinavir/ritonavir with ABC/3TC [3]. The HEAT team did not speculate on the reasons for worse virologic responses in African Americans and women in either trial and did not mention the potential impact of adherence on these findings.
References
1. Smith KY, Kumar PN, Patel P, et al. Differences in virologic response among African-Americans and females regardless of therapy in the HEAT study. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract MOPEB033.
2. Smith KY, Patel P, Fine D, et al. Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. AIDS. 2009 Jun 17. Epub ahead of print.
3. DeJesus J, Gathe J, Katlama C, et al. Virologic response and tolerability by sex and race in subjects receiving fosamprenavir/ritonavir BID and lopinavir/ritonavir BID, each in combination with abacavir/lamivudine D (the KLEAN study). 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 22-25. Sydney. Abstract WEPEB041.
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