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Providing antiretroviral therapy (ART) to HIV-infected individuals reduces the likelihood of HIV transmission, but how strong is the effect within serodiscordant couples, and how early should ART be provided to maximize the benefit? A post hoc analysis from the Partners in Prevention HSV/HIV Transmission Study (previously described at CROI 2010) provides some answers.
The study involved 3381 heterosexual serodiscordant couples in Africa. Researchers compared transmission rates between the 349 HIV-infected individuals who initiated ART during follow-up (mostly because of pregnancy or low CD4-cell counts) and the 3032 who did not. Of those who initiated ART, 70% achieved viral loads <2.4 log copies/mL. All study participants were counseled frequently about safe sex; unprotected sex was reported at only 7% of all follow-up visits.
A total of 103 genetically linked transmission events occurred, but only one was in a couple in which the infected partner was receiving ART. The transmission rate was 0.37 per 100 person-years among individuals who initiated ART (95% confidence interval, 0.09–2.04) versus 2.24 per 100 person-years among those who did not (95% CI, 1.84–2.72) — a difference that translates into a 92% risk reduction with ART.
Among individuals who were not receiving ART, the rate of transmission was highest for those with CD4 counts <200 cells/mm3; for those with CD4 counts >200 cells/mm3, the rate of transmission was highest for those with a viral load >50,000 copies/mL.
Donnell D et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: A prospective cohort analysis. Lancet 2010 May 27; [e-pub ahead of print]. (http://bit.ly/ac201006071a)
Dabis F et al. HIV drugs for treatment, and for prevention. Lancet 2010 May 27; [e-pub ahead of print]. (http://bit.ly/ac201006072b)
Comment
This study clearly demonstrates that the risk for HIV transmission is highest among individuals with CD4 counts <200 cells/mm3 — but it also identifies another high-risk group: patients with CD4 counts >200 cells/mm3 who have viral loads >50,000 copies/mL. If similar results are found in ongoing randomized trials (e.g., HIV Prevention Trials Network study 052), one could argue that ART should be offered to every person who has either a CD4 count <200 cells/mm3 or a viral load >50,000 copies/mL. Obviously, the concept of treating people with a CD4 count <200 cells/mm3 is not new, but the idea of using viral load to prioritize ART initiation among people with CD4 counts >200 cells/mm3 is provocative. Unfortunately, in most of the developing world, viral loads cannot be measured readily at the point of care — a problem that requires urgent attention.