title: Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial.
abstract: BACKGROUND
  Herpes simplex virus type 2 (HSV-2) infection is common among human immunodeficiency virus (HIV)-infected persons, and HSV reactivation increases plasma and genital HIV-1 levels. We studied HIV-1 levels during HSV suppression in coinfected persons in a placebo-controlled crossover trial.
  
  
  METHODS
  Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2-seropositive men who have sex with men in Lima, Peru, with CD4 cell counts >200 cells/ microL were randomized to receive either valacyclovir at 500 mg twice daily or placebo for 8 weeks, after which they underwent a 2-week washout period and then received the alternative regimen for 8 weeks. Specimens included daily anogenital swabs (for HSV DNA polymerase chain reaction [PCR]), thrice weekly rectal mucosal secretions (for HIV-1 RNA and HSV DNA PCR) obtained by anoscopy, and weekly plasma (for HIV-1 RNA PCR). Outcomes were rectal and plasma HIV-1 RNA levels by treatment arm.
  
  
  RESULTS
  HIV-1 was detected in 73% of 844 rectal and 99% of 288 plasma specimens. HSV was detected in 29% and 4% of mucocutaneous specimens obtained during placebo and valacyclovir administration, respectively (P<.001). Valacyclovir resulted in a 0.16 (95% confidence interval [CI], 0.07-0.25; P=.0008; 33% decrease) log(10) copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI, 0.23-0.42; P<.0001; 53% decrease) log(10) copies/mL lower plasma HIV-1 level, compared with values for placebo.
  
  
  CONCLUSIONS
  Valacyclovir significantly reduces rectal and plasma HIV-1 levels in HIV-1/HSV-2-coinfected men. HSV suppression may provide clinical benefits to persons not receiving highly active ART as well as public health benefits.
authors.affiliation: Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. ccelum@u.washington.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: Sanchez
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coombs
authors.forename: Rosario
authors.initials: R
authors.lastname: Zuñiga
authors.forename: Amalia S
authors.initials: AS
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 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000821:virology*; D015497:HIV-1 / Q000235:genetics; D006561:Herpes Simplex / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000235:genetics; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D012007:Rectum / Q000821:virology; D016896:Treatment Outcome; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir