Valacyclovir decreases plasma HIV-1 RNA in HSV-2 seronegative individuals: A randomized placebo-controlled crossover trial

Christophe Vanpouille, Andrea Lisco, Jean-Charles B. Grivel, Leda C. Bassit, Robert C. Kauffman, Jorge Sanchez, Raymond F. Schinazi, Michael M. Lederman, Benigno Rodriguez, Leonid Margolis

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Abstract

Background. Acyclovir (ACV), a highly specific anti-herpetic drug, acts as a DNA chain terminator for several human herpesviruses (HHVs), including HHV-2 (HSV-2), a common human immunodeficiency virus (HIV)-1 co-pathogen. Several trials demonstrated that HSV-2 suppressive therapy using ACV or its prodrug valacyclovir (valACV) reduced plasma HIV-1 viral load (VL) in HIV-1/HSV-2 coinfected persons, and this was proposed to be due to a decrease in generalized immune activation. Recently, however, we found that ACV directly suppresses HIV-1 ex vivo in tissues free of HSV-2 but endogenously coinfected with other HHVs. Here, we asked whether valACV suppresses VL in HIV-1 infected HSV-2-seronegative persons. Methods. Eighteen HIV-1 infected HSV-2-seronegative individuals were randomly assigned in a double blind placebo-controlled, crossover trial. Eligible participants had CD4 cell counts of ≥ 500 cells/μL and were not taking antiretroviral therapy. Subjects in group A received 12 weeks of valACV 500 mg given twice daily by mouth followed by 2 weeks of a no treatment washout and then 12 weeks of placebo; subjects in group B received 12 weeks of placebo followed by 2 weeks of no treatment washout and then 12 weeks of valACV 500 mg twice daily. Results. HIV-1 VL in plasma of patients treated with valACV 500 mg twice daily for 12 weeks was reduced on average by 0.37 log10 copies/mL. Conclusions. These data indicate that the effects of valACV on HIV-1 replication are not related to the suppression of HSV-2-mediated inflammation and are consistent with a direct effect of ACV on HIV-1 replication.

Original languageEnglish
Pages (from-to)1708-1714
Number of pages7
JournalClinical Infectious Diseases
Volume60
Issue number11
DOIs
Publication statusPublished - 1 Jun 2015
Externally publishedYes

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Keywords

  • acyclovir
  • herpesvirus
  • HIV-1
  • HSV-2
  • reverse transcriptase inhibitor

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Vanpouille, C., Lisco, A., Grivel, J-C. B., Bassit, L. C., Kauffman, R. C., Sanchez, J., Schinazi, R. F., Lederman, M. M., Rodriguez, B., & Margolis, L. (2015). Valacyclovir decreases plasma HIV-1 RNA in HSV-2 seronegative individuals: A randomized placebo-controlled crossover trial. Clinical Infectious Diseases, 60(11), 1708-1714. https://doi.org/10.1093/cid/civ172