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
Background Epidemiologic data suggest that infection with herpessimplex virus type 2 (HSV-2) is associated with increased genitalshedding of human immunodeficiency virus type 1 (HIV-1) RNAand HIV-1 transmissibility.
Methods We conducted a randomized, double-blind, placebo-controlledtrial of HSV suppressive therapy with valacyclovir (at a doseof 500 mg twice daily) in Burkina Faso among women who wereseropositive for HIV-1 and HSV-2; all were ineligible for highlyactive antiretroviral therapy. The patients were followed for24 weeks (12 weeks before and 12 weeks after randomization).Regression models were used to assess the effect of valacycloviron the presence and quantity of genital and plasma HIV-1 RNAand genital HSV-2 DNA during treatment, adjusting for baselinevalues, and to evaluate the effect over time.
Results A total of 140 women were randomly assigned to treatmentgroups; 136 were included in the analyses. At enrollment, themedian CD4 cell count was 446 cells per cubic millimeter, andthe mean plasma viral load was 4.44 log10 copies per milliliter.With the use of summary-measures analysis, valacyclovir therapywas found to be associated with a significant decrease in thefrequency of genital HIV-1 RNA (odds ratio, 0.41; 95% confidenceinterval [CI], 0.21 to 0.80) and in the mean quantity of thevirus (log10 copies per milliliter, –0.29; 95% CI, –0.44to –0.15). However, there was no significant decreasein detection of HIV (risk ratio, 0.93; 95% CI, 0.81 to 1.07).HSV suppressive therapy also reduced the mean plasma HIV-1 RNAlevel by 0.53 log10 copy per milliliter (95% CI, –0.72to –0.35). Repeated-measures analysis showed that theseeffects became significantly stronger during the 3 months offollow-up.
Conclusions HSV suppressive therapy significantly reduces genitaland plasma HIV-1 RNA levels in dually infected women. This findingmay have important implications for HIV control. (ClinicalTrials.govnumber, NCT00158509
[ClinicalTrials.gov]
.)
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 n_nagot{at}hotmail.com.
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