Decreased monocyte activation with daily acyclovir use in HIV-1/HSV-2 coinfected women

Sex Transm Infect. 2015 Nov;91(7):485-8. doi: 10.1136/sextrans-2014-051867. Epub 2015 Apr 22.

Abstract

Objectives: Several clinical trials have demonstrated that daily treatment of HIV-infected individuals with the antiherpes drug acyclovir slightly decreases HIV-1 viral load and slows disease progression. This study examines if this slowing in clinical progression is a direct cause of the decrease in viral load or an indirect effect of lower immune activation due to lower levels of herpetic reactivation.

Methods: Women who participated in a randomised clinical trial of daily acyclovir use (n=301) were monitored every 6 months for changes in immune activation. Soluble CD14 (sCD14), a marker for monocyte activation, and C-reactive protein (CRP), a marker for general immune activation, were measured by ELISA.

Results: Initial levels of sCD14 and CRP were not predictive of HIV disease progression when controlling for initial CD4+ cell count and HIV viral load. sCD14 levels, but not CRP, decreased in the acyclovir treatment arm at a significantly faster rate than the placebo group, which was independent of changes in HIV viral load and CD4+ cell count in a multivariant mixed-effects model (p=0.039). However, the magnitude of this decrease was relatively small with a total estimated decrease of sCD14 of 15% of initial levels.

Conclusions: These data suggest that decreased monocyte activation may play a minor role in the ability of daily acyclovir use to slow HIV disease progression.

Clinical trial registration number: NCT00405821.

Keywords: HERPES; HERPES SIMPLEX (CLINICAL); HIV; HIV IMMUNOLOGY; HSV THERAPEUTICS.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Acyclovir / therapeutic use*
  • Adult
  • Antiviral Agents / therapeutic use*
  • C-Reactive Protein / analysis
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1 / isolation & purification
  • Herpes Genitalis / complications*
  • Herpes Genitalis / drug therapy*
  • Herpes Genitalis / immunology
  • Herpesvirus 2, Human / isolation & purification
  • Humans
  • Lipopolysaccharide Receptors / blood
  • Middle Aged
  • Monocytes / chemistry
  • Monocytes / immunology*
  • Young Adult

Substances

  • Antiviral Agents
  • Lipopolysaccharide Receptors
  • C-Reactive Protein
  • Acyclovir

Associated data

  • ClinicalTrials.gov/NCT00405821