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HIV/HSV-2 Coinfection: Disappointing Results for Acyclovir Suppression

HSV-2 suppression with acyclovir did not reduce the risk for HIV transmission.

Herpes simplex virus (HSV)-2 coinfection is associated with increased plasma and genital-tract HIV RNA levels and may increase the risk for HIV transmission. Many experts have believed that suppressing HSV-2 reactivation might reduce the likelihood of HIV transmission. To assess this possibility, investigators studied heterosexual couples in which one partner was HIV uninfected and the other was both HIV and HSV-2 seropositive — with CD4 counts 250 cells/mm³ and no current antiretroviral therapy (ART). The infected partners were randomized to receive oral acyclovir or placebo for up to 24 months.

A total of 3408 couples in southern and East Africa were enrolled. HIV seroconversion occurred in 132 initially uninfected partners. HIV sequencing revealed that 29% of transmissions were not genetically linked within couples, suggesting that these infections were acquired from a person who was not in the study. Of 84 genetically linked transmissions included in the analysis, 41 occurred in the acyclovir group and 43 in the placebo group (hazard ratio, 0.92; P=0.69). (Seven additional linked infections were excluded — 6 because they occurred while HIV-infected women were pregnant and not taking the study drug and 1 because an incorrect drug was dispensed.) The mean plasma HIV RNA level during the follow-up period was 0.25 log₁₀ copies/mL lower in the acyclovir group than in the placebo group (P<0.001). As expected, acyclovir use substantially lowered the risk for genital ulcers (risk ratio for HSV-2–positive ulceration, 0.27).

Comment: Although acyclovir use reduced plasma HIV RNA levels and the incidence of genital ulcer disease in HSV-2 coinfected patients, it did not decrease the likelihood of HIV transmission. Why didn't acyclovir suppression work? One possibility, discussed by the authors, is that the extent of HIV RNA reduction conferred by acyclovir use was insufficient to prevent HIV transmission (although it may be enough to slow progression of HIV disease [5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, 2009, abstract WeLBC102]).

New strategies to reduce the risk for HIV transmission in serodiscordant couples are needed. One such approach, currently under study, is to initiate ART in infected partners, even when they don't meet other treatment criteria, with the goal of lowering HIV RNA levels and thereby preventing transmission.

— Rajesh T. Gandhi, MD

Published in Journal Watch Infectious Diseases January 20, 2010

Citation(s):

Celum C et al. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med 2010 Jan 20; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa0904849)

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