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Decreased monocyte activation with daily acyclovir use in HIV-1/HSV-2 coinfected women
  1. Andrew D Redd1,2,
  2. Kevin Newell3,
  3. Eshan U Patel1,
  4. Fred Nalugoda4,
  5. Paschal Ssebbowa4,
  6. Sarah Kalibbala4,
  7. Melanie A Frank1,
  8. Aaron A R Tobian5,
  9. Ronald H Gray6,
  10. Thomas C Quinn1,2,
  11. David Serwadda4,7,
  12. Steven J Reynolds1
  1. 1Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
  2. 2Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  3. 3Frederick National Laboratory for Cancer Research, Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick, Maryland, USA
  4. 4Rakai Health Sciences Program, Entebbe, Uganda
  5. 5Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  6. 6Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
  7. 7Institute of Public Health, Makerere University, Kampala, Uganda
  1. Correspondence to Dr Steven J Reynolds, NIAID/NIH ICER Program, US Embassy, P.O. Box 7007, Kampala, Uganda; sjreynolds{at}niaid.nih.gov

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

  • HERPES
  • HERPES SIMPLEX (CLINICAL)
  • HIV
  • HIV IMMUNOLOGY
  • HSV THERAPEUTICS

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