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A Tale of Two Viruses: HSV-2 and HIV

Suppression of HSV-2 reactivation with valacyclovir reduces genital and plasma HIV levels.

Herpes simplex virus (HSV)-2 coinfection is associated with increased genital HIV shedding, which may increase transmissibility of HIV. Might suppressing HSV reactivation with antiviral therapy reduce genital HIV shedding? To address this question, investigators randomized 140 HIV/HSV-2–seropositive women in Burkina Faso to receive 12 weeks of either valacyclovir (500 mg twice daily) or placebo. The women were ineligible for potent antiretroviral therapy according to WHO recommendations for resource-scarce countries, mainly because of high CD4 counts (median, 446 cells/mm³).

During the 12 weeks before randomization, genital and plasma HIV RNA levels were higher in women with detectable genital HSV-2 than in those who never shed HSV-2. As expected, valacyclovir reduced genital HSV-2 shedding and genital ulcerations. During the 12 weeks of treatment, the valacyclovir group had a significantly lower frequency of detectable genital HIV RNA (odds ratio, 0.41; 95% confidence interval, 0.21–0.80) and a significantly lower mean quantity of genital HIV RNA (mean reduction, 0.29 log₁₀ copies/mL) than did the placebo group. In addition, the mean plasma HIV RNA level was lower in the valacyclovir group than in the placebo group (mean reduction, 0.53 log₁₀ copies/mL). The between-group differences in all three measures increased steadily during the 12-week treatment period.

Comment: HIV transmission may be affected by factors that influence genital-tract HIV RNA levels, such as HSV-2 coinfection. These findings show that suppressing HSV-2 reactivation with valacyclovir reduces genital-tract shedding of HIV and plasma HIV RNA levels. The million-dollar question is whether HSV-suppressive therapy can reduce HIV transmission; studies to address this question are ongoing.

— Rajesh T. Gandhi, MD

Published in Journal Watch Infectious Diseases February 21, 2007

Citation(s):

Nagot N et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med 2007 Feb 22; 356:790-9.

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