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HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men.

Zuckerman, Richard A and Lucchetti, Aldo and Whittington, William L H and Sánchez, Jorge and Coombs, Robert W and Magaret, Amalia and Wald, Anna and Corey, Lawrence and Celum, Connie (2009) HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men. AIDS (London, England), 23 (4). pp. 479-483. ISSN 1473-5571

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Abstract

OBJECTIVES: Suppressive herpes simplex virus (HSV) therapy can decrease plasma, cervical, and rectal HIV-1 levels in HIV-1/HSV-2 co-infected persons. We evaluated the effect of HSV-2 suppression on seminal HIV-1 levels. DESIGN: Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2 men who have sex with men (MSM) in Lima, Peru, with CD4 >200 cells/microl randomly received valacyclovir 500 mg twice daily or placebo for 8 weeks, then the alternative regimen for 8 weeks after a 2-week washout. Peripheral blood and semen specimens were collected weekly. Anogenital swab specimens for HSV DNA were self-collected daily and during clinic visits. METHODS: HIV-1 RNA was quantified in seminal and blood plasma by TaqMan real-time polymerase chain reaction (RT-PCR) or Roche Amplicor Monitor assays. HSV and seminal cytomegalovirus (CMV) were quantified by RT-PCR. Linear mixed models examined differences within participants by treatment arm. RESULTS: Median CD4 cell count of participants was 424 cells/microl. HIV-1 was detected in 71% of 231 semen specimens. HSV was detected from 29 and 4.4% of swabs on placebo and valacyclovir, respectively (P < 0.001). Valacyclovir significantly reduced the proportion of days with detectable seminal HIV-1 (63% during valacyclovir vs. 78% during placebo; P = 0.04). Seminal HIV-1 quantity was 0.25 log10 copies/ml lower [95% confidence interval (CI) -0.40 to -0.10; P = 0.001] during the valacyclovir arm compared with placebo, a 44% reduction. CD4 cell count (P = 0.32) and seminal cellular CMV quantity (P = 0.68) did not predict seminal plasma HIV-1 level. CONCLUSIONS: Suppressive valacyclovir reduced seminal HIV-1 levels in HIV-1/HSV-2 co-infected MSM not receiving ART. The significance of this finding will be evaluated in a trial with HIV-1 transmission as the outcome.

Item Type: Article
Additional Information: This is a non-final version of an article published in final form in Aids (2009) 23(4):479-83.
DOI: 10.1097/QAD.0b013e328326ca62
PubMed ID: 19169140
NIHMSID: NIHMS109754
PMCID: PMC2707902
Grant Numbers: P30 AI027757-21, U01 AI038858-08, P01 AI030731-18, R37 AI042528-11
Keywords or MeSH Headings: Acyclovir/analogs & derivatives/pharmacology; Adult; Antiviral Agents/pharmacology; CD4 Lymphocyte Count; Cross-Over Studies; Double-Blind Method; HIV Infections/complications/transmission/virology; HIV-1/*drug effects/isolation & purification; Herpes Genitalis/*complications/drug therapy/transmission/virology; Herpesvirus 2, Human/*drug effects/isolation & purification; *Homosexuality, Male; Humans; Male; Middle Aged; RNA, Viral/analysis; Semen/*virology; Valine/analogs & derivatives/pharmacology; Viral Load; Young Adult
Subjects: Organisms > Viruses > RNA viruses
Diseases > Viral diseases
Therapeutics > Drug Therapy
Depositing User: Library Staff
Date Deposited: 28 Sep 2009 18:42
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/273

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