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

TitleDecreased monocyte activation with daily acyclovir use in HIV-1/HSV-2 coinfected women
Publication TypeJournal Article
Year of Publication2015
AuthorsRedd, AD, Newell, K, Patel, EU, Nalugoda, F, Ssebbowa, P, Kalibbala, S, Frank, MA, Tobian, AA, Gray, RH, Quinn, TC, Serwadda, D, Reynolds, SJ
JournalSex Transm Infect
Date PublishedNov
Type of ArticleArticle
ISBN Number1472-3263 (Electronic)1368-4973 (Linking)
Accession Number25904747
KeywordsAcyclovir/*therapeutic use, Adult, Antigens, CD14/blood, Antiviral Agents/*therapeutic use, C-Reactive Protein/analysis, Disease Progression, Enzyme-Linked Immunosorbent Assay, Female, Herpes, Herpes Genitalis/*complications/*drug therapy/immunology, Herpes simplex (clinical), Herpesvirus 2, Human/isolation & purification, HIV, Hiv immunology, HIV Infections/*complications/*drug therapy/immunology, HIV-1/isolation & purification, Hsv therapeutics, Humans, Middle Aged, Monocytes/chemistry/*immunology, Young Adult

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.