title: Decreased monocyte activation with daily acyclovir use in HIV-1/HSV-2 coinfected women.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  NCT00405821.
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.affiliation: Frederick National Laboratory for Cancer Research, Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick, Maryland, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Newell
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Eshan U
authors.initials: EU
authors.lastname: Patel
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Fred
authors.initials: F
authors.lastname: Nalugoda
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Paschal
authors.initials: P
authors.lastname: Ssebbowa
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kalibbala
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Frank
authors.affiliation: Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Aaron A R
authors.initials: AA
authors.lastname: Tobian
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda Institute of Public Health, Makerere University, Kampala, Uganda.
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use*; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000302:isolation & purification; D006558:Herpes Genitalis / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000302:isolation & purification; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D018950:Lipopolysaccharide Receptors; D002097:C-Reactive Protein; D000212:Acyclovir
keywords: HERPES; HERPES SIMPLEX (CLINICAL); HIV; HIV IMMUNOLOGY; HSV THERAPEUTICS