title: High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose acyclovir in persons coinfected with HIV-1 and HSV-2: a randomized crossover trial.
abstract: BACKGROUND
  Standard doses of herpes simplex virus (HSV) suppressive therapy reduce plasma HIV-1 RNA levels (0.25-0.53 log10 copies per milliliter) among HIV-1/HSV-2 coinfected persons. Postulated mechanisms for this effect include direct inhibition of HIV-1 by acyclovir or indirect reduction by decreasing HSV-associated inflammation. We hypothesized that high-dose valacyclovir would further reduce plasma HIV-1 RNA and that the effect would be mediated by greater suppression of HSV shedding.
  
  
  METHODS
  Thirty-four participants with HIV-1 and HSV-2 not on antiretroviral therapy were enrolled into a randomized, open-label crossover trial of valacyclovir 1000 mg twice daily or acyclovir 400 mg twice daily for 12 weeks, followed by a 2-week washout, and then the alternate treatment arm for 12 weeks. HSV DNA was measured from daily self-collected genital swabs for the initial 4 weeks of each arm, and HIV-1 RNA was quantified from weekly plasma samples.
  
  
  RESULTS
  Twenty-eight participants provided plasma samples and genital swabs on both acyclovir and valacyclovir. The genital HSV-2 shedding rate was the same on valacyclovir and acyclovir [7.8% vs. 8.2% of days; relative risk: 0.95; 95% confidence interval (CI): 0.66 to 1.37; P = 0.78]. Plasma HIV-1 RNA was 0.27 log10 copies per milliliter lower on valacyclovir compared with acyclovir (95% CI: -0.41 to -0.14 log10 copies per milliliter; P < 0.001); this was unchanged after adjustment for genital HSV-2 shedding.
  
  
  CONCLUSIONS
  High-dose valacyclovir reduces plasma HIV-1 RNA levels more than standard-dose acyclovir in HIV-1/HSV-2-seropositive persons not receiving antiretroviral therapy. The incremental reduction in plasma HIV-1 RNA achieved is not mediated by greater genital HSV-2 suppression.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98104, USA. tarap@u.washington.edu
authors.forename: Tara
authors.initials: T
authors.lastname: Perti
authors.forename: Misty
authors.initials: M
authors.lastname: Saracino
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
authors.forename: Kurt
authors.initials: K
authors.lastname: Diem
authors.forename: Negusse
authors.initials: N
authors.lastname: Ocbamichael
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.forename: Stacy
authors.initials: S
authors.lastname: Selke
authors.forename: Amalia
authors.initials: A
authors.lastname: Magaret
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D060085:Coinfection; D018592:Cross-Over Studies; D003587:Cytomegalovirus / Q000235:genetics; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006558:Herpes Genitalis / Q000150:complications* / Q000188:drug therapy; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019562:Viral Load; D017201:Virus Shedding / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir
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