Reduction of HIV-1 RNA Levels with Therapy to Suppress Herpes Simplex Virus

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The New England Journal of Medicine
Volume 356, 790-799 February 22, 2007 Number 8

Reduction of HIV-1 RNA Levels with Therapy to Suppress Herpes Simplex Virus

Nicolas Nagot, M.D., Abdoulaye Ouédraogo, M.D., Vincent Foulongne, Ph.D., Issouf Konaté, M.D., Helen A. Weiss, Ph.D., Laurence Vergne, Ph.D., Marie-Christine Defer, Ph.D., Didier Djagbaré, M.Sc., Anselme Sanon, M.Sc., Jean-Baptiste Andonaba, M.D., Pierre Becquart, Ph.D., Michel Segondy, Ph.D., Roselyne Vallo, M.Sc., Adrien Sawadogo, M.D., Philippe Van de Perre, M.D., Ph.D., Philippe Mayaud, M.D., for the ANRS 1285 Study Group


ABSTRACT

Background Epidemiologic data suggest that infection with herpes simplex virus type 2 (HSV-2) is associated with increased genital shedding of human immunodeficiency virus type 1 (HIV-1) RNA and HIV-1 transmissibility.

Methods We conducted a randomized, double-blind, placebo-controlled trial of HSV suppressive therapy with valacyclovir (at a dose of 500 mg twice daily) in Burkina Faso among women who were seropositive for HIV-1 and HSV-2; all were ineligible for highly active antiretroviral therapy. The patients were followed for 24 weeks (12 weeks before and 12 weeks after randomization). Regression models were used to assess the effect of valacyclovir on the presence and quantity of genital and plasma HIV-1 RNA and genital HSV-2 DNA during treatment, adjusting for baseline values, and to evaluate the effect over time.

Results A total of 140 women were randomly assigned to treatment groups; 136 were included in the analyses. At enrollment, the median CD4 cell count was 446 cells per cubic millimeter, and the mean plasma viral load was 4.44 log10 copies per milliliter. With the use of summary-measures analysis, valacyclovir therapy was found to be associated with a significant decrease in the frequency of genital HIV-1 RNA (odds ratio, 0.41; 95% confidence interval , 0.21 to 0.80) and in the mean quantity of the virus (log10 copies per milliliter, –0.29; 95% CI, –0.44 to –0.15). However, there was no significant decrease in detection of HIV (risk ratio, 0.93; 95% CI, 0.81 to 1.07). HSV suppressive therapy also reduced the mean plasma HIV-1 RNA level by 0.53 log10 copy per milliliter (95% CI, –0.72 to –0.35). Repeated-measures analysis showed that these effects became significantly stronger during the 3 months of follow-up.

Conclusions HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women. This finding may have important implications for HIV control. (ClinicalTrials.gov number, NCT00158509 http://content.nejm.org/cgi/external_ref?access_num=NCT00158509&link_type=CLINTRIALGOV .)

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Source Information

From the Centre Muraz (N.N., A.O., I.K., L.V., M.-C.D., D.D., A. Sanon, R.V.) and University Hospital (J.-B.A., A. Sawadogo) — both in Bobo-Dioulasso, Burkina Faso; the London School of Hygiene and Tropical Medicine, London (N.N., H.A.W., P.M.); and Montpellier University Hospital and Research Unit 145, Montpellier, France (V.F., P.B., M.S., P.V.P.).

Address reprint requests to Dr. Nagot at the Clinical Research Unit, London School of Hygiene and Tropical Medicine, Keppel St., London WC1E 7HT, United Kingdom, or at [e-mail].

<complete article at:>
http://content.nejm.org/cgi/content/full/356/8/790?query=TOC

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