title: HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA. richard.a.zuckerman@dartmouth.edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Zuckerman
authors.forename: Aldo
authors.initials: A
authors.lastname: Lucchetti
authors.forename: William L H
authors.initials: WL
authors.lastname: Whittington
authors.forename: Jorge
authors.initials: J
authors.lastname: Sánchez
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coombs
authors.forename: Amalia
authors.initials: A
authors.lastname: Magaret
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015658:HIV Infections / Q000150:complications / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006558:Herpes Genitalis / Q000150:complications* / Q000188:drug therapy / Q000635:transmission / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000302:isolation & purification; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D012661:Semen / Q000821:virology*; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir