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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

valacyclovir
Human Herpesvirus 2
Cross-Over Studies
HIV-1
Placebos
RNA
Acyclovir
Viral Load
Herpesviridae
Virus Replication
Prodrugs

Keywords

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

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Valacyclovir decreases plasma HIV-1 RNA in HSV-2 seronegative individuals : A randomized placebo-controlled crossover trial. / Vanpouille, Christophe; Lisco, Andrea; Grivel, Jean-Charles B.; Bassit, Leda C.; Kauffman, Robert C.; Sanchez, Jorge; Schinazi, Raymond F.; Lederman, Michael M.; Rodriguez, Benigno; Margolis, Leonid.

In: Clinical Infectious Diseases, Vol. 60, No. 11, 01.06.2015, p. 1708-1714.

Research output: Contribution to journalArticle

Vanpouille, C, Lisco, A, Grivel, J-CB, Bassit, LC, Kauffman, RC, Sanchez, J, Schinazi, RF, Lederman, MM, 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, vol. 60, no. 11, pp. 1708-1714. https://doi.org/10.1093/cid/civ172
Vanpouille, Christophe ; Lisco, Andrea ; Grivel, Jean-Charles B. ; Bassit, Leda C. ; Kauffman, Robert C. ; Sanchez, Jorge ; Schinazi, Raymond F. ; Lederman, Michael M. ; Rodriguez, Benigno ; Margolis, Leonid. / Valacyclovir decreases plasma HIV-1 RNA in HSV-2 seronegative individuals : A randomized placebo-controlled crossover trial. In: Clinical Infectious Diseases. 2015 ; Vol. 60, No. 11. pp. 1708-1714.
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