Top 10 HIV/AIDS-Related Clinical Developments of 2011
December 1, 2011
The literature on racial and gender differences in the clinical outcomes of those treated with ART poses more questions than answers. It is a complicated science and when looking at race, the data must be evaluated in the context of an overall increased risk for poorer outcomes among African Americans than for whites in the general population. Since the introduction of potent combination ART, mortality rates among HIV-positive persons have declined substantially for all, but the benefits have been uneven with African Americans, especially African-American women, seeing smaller gains in survival.
Race can be a marker for other factors that influence well-being, including access to health care, insurance availability, and the stress that has been associated with being black in America, among others. According to one important model, much of the racial disparity in HIV outcomes can be explained by a later start of ART and an increased rate of treatment discontinuation for blacks compared to whites.8
An analysis of data from the Women's Interagency HIV Study (WIHS) and the all-male Multicenter AIDS Cohort Study (MACS) found that HIV-RNA levels were 30 percent to 50 percent higher in men than in women, but that women experienced disease progression at lower viral loads.9 However, although most of the women in WIHS are non-white and the majority of the men in MACS are white, the role of race was not examined.
The AIDS Clinical Trials Group (ACTG) study A5202 provides an opportunity to address gender and race disparities on the (more) level playing field of a clinical trial.10 A5202 was a four-arm study looking at the efficacy and safety of Truvada versus Epzicom (abacavir/3TC, Kivexa) in combination with either Sustiva (efavirenz, Stocrin) or Norvir (ritonavir)-boosted Reyataz (atazanavir).
There were 1,857 participants enrolled from sites across the U.S. Of these, 17 percent were women, 40 percent white non-Hispanic, 33 percent black non-Hispanic, and 23 percent Hispanic. As predicted by the model mentioned above, blacks did have a lower baseline CD4+ cell count (24 percent versus 13 percent with less than 50 cells/µL, P < .001), although viral load was also lower for blacks (63 percent versus 46 percent with less than 50,000 copies/mL, P < .001) than whites (perhaps because a greater proportion of black participants were women).
During the study, black participants had a higher risk of virologic failure compared to whites and Hispanics (for whom outcomes were similar); however, there was no significant difference in the time to failure between men and women. It was when looking at the specific regimens that major differences in virologic outcomes became apparent.
Women assigned to Reyataz+Norvir had a higher risk for virologic failure with either nucleoside reverse transcriptase inhibitor (NRTI) backbone than women assigned to Sustiva and compared to men assigned Reyataz+Norvir. Interestingly, comparing Reyataz+Norvir to Sustiva, there was no significant difference in time to safety/tolerability events by gender.
Women did have an increased risk of moderate to severe toxicity with Epzicom compared to men receiving these NRTIs. Blacks, but not Hispanics, had an increased risk of a tolerability endpoint with either Reyataz+Norvir or Sustiva compared to whites (1.37 [1.44 to 1.65] P = .0007).
Self-reported adherence at two months was high overall (92 percent with 100 percent adherence) and did not differ significantly by gender. However, blacks, but not Hispanics, were more likely to report less than 100 percent adherence than whites, with the percentage reporting less than 100 percent adherence about double for blacks compared to whites.
The Bottom Line
This large, randomized trial presents fascinating data on differences in outcomes with commonly used ART regimens by gender and race. As seen before, blacks did not fare as well, possibly related to suboptimal adherence and greater rates of overall medication intolerance. For women, the key finding was that Reyataz+Norvir was not as well tolerated as Sustiva. There is speculation that women do not tolerate Norvir as well as men. In fact, in the ACTG study A5175, where Reyataz without Norvir was studied, women were not found to have higher rates of treatment failure compared to men and there were no gender differences in tolerability.
These data raise an important question regarding the need to tailor therapy based on patient characteristics. If women do indeed tend to have a greater intolerance to Norvir, then effective regimens that spare this protease inhibitor may be preferred. Studies have demonstrated the efficacy of unboosted Reyataz, but these have not provided much traction for such an approach in clinical practice -- likely due to the sense of security Norvir boosting provides against drug resistance and the need to use Epzicom instead of Truvada given the effect of Viread on Reyataz levels. If Norvir is not women-friendly, this strategy will need to be reconsidered.
The lower adherence rates and greater intolerance to the protease inhibitor and non-nucleoside among black participants in this trial also require greater scrutiny. Much of the adherence intervention literature is now dated and new ways of thinking are needed to support the care of people living with HIV today. African Americans, especially young black MSM, are at the greatest risk for HIV in the U.S. and face challenges to successful management of HIV that are unique. All the evidence points to poverty, discrimination, and other structural mega-factors as having a tremendous role in the chance for success -- problems that cannot be countered solely with a series of counseling sessions, electronic reminders or co-formulated medications. If anything, the A5202 data make it clear that there are differences in ART response by race and gender. The challenge now is what to do about it.
This article was provided by TheBody.
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