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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 Aa; Lucchetti, Aldob; Whittington, William LHc; Sánchez, Jorgeb; Coombs, Robert Wc,d; Magaret, Amaliad,f; Wald, Annac,d,e,f; Corey, Lawrencec,d,f; Celum, Conniec,e,g

doi: 10.1097/QAD.0b013e328326ca62
Clinical Science: Concise Communication

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/μl 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/μl. 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.

aSection of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA

bAsociación Civil Impacta Salud y Educación, Lima, Peru

cDepartment of Medicine, USA

dDepartment of Laboratory Medicine, USA

eDepartment of Epidemiology, University of Washington, Seattle, USA

fVaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, USA

gDepartment of Global Health, University of Washington, Seattle, Washington, USA.

Received 7 October, 2008

Revised 25 November, 2008

Accepted 3 December, 2008

Correspondence to Richard A. Zuckerman, MD, MPH, Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA. Tel: +1 603 650 6060; fax: +1 603 650 6110; e-mail: richard.a.zuckerman@dartmouth.edu

© 2009 Lippincott Williams & Wilkins, Inc.