title: High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial.
abstract: BACKGROUND
  Standard-dose HSV-2 suppressive therapy (acyclovir 400 mg twice daily) reduces plasma HIV-1 levels by 0.25-0.50 log(10) copies/mL. It is not known if higher doses might further suppress HIV-1 levels.
  
  
  METHODS
  We enrolled 32 HIV-1/HSV-2 dually infected Kenyan individuals who were not on antiretroviral therapy (ART) into a randomized, crossover trial of 2 dosing regimens of HSV-2 suppression: valacyclovir 1.5 g vs acyclovir 400 mg, both twice daily for 12 weeks, then a 2-week washout, and then the alternative for 12 weeks. Weekly plasma HIV-1 RNA quantity was measured (ClinicalTrials.gov number NCT01026454).
  
  
  RESULTS
  Mean plasma HIV-1 levels were significantly lower on valacyclovir compared with acyclovir: 2.94 vs 3.56 log(10) copies/mL, an average difference of 0.62 log(10) copies/mL (95% confidence interval [CI]: -0.68, -0.55; P < .001), a 76% decrease. Valacyclovir resulted in a 1.23 log(10) copies/mL decrease compared with baseline HIV-1 levels without HSV-2 suppression. Adherence was similar (99.4% of dispensed study tablets taken), and high-dose valacyclovir was well tolerated.
  
  
  CONCLUSIONS
  High-dose valacyclovir reduced plasma HIV-1 viral levels by 0.62 log(10) copies/mL compared with standard-dose acyclovir. The potential for higher-dose HSV-2 suppressive therapy to slow HIV-1 disease progression and reduce HIV-1 infectiousness among HIV-1/HSV-2 coinfected persons not yet eligible for ART warrants further evaluation.
authors: Infectious Diseases Institute, Makerere University, Kampala, Uganda.
authors: Kenneth
authors: K
authors: Mugwanya
authors: Jared M
authors: JM
authors: Baeten
authors: Nelly R
authors: NR
authors: Mugo
authors: Elizabeth
authors: E
authors: Irungu
authors: Kenneth
authors: K
authors: Ngure
authors: Connie
authors: C
authors: Celum
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D060085:Coinfection; D018592:Cross-Over Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism*; D006558:Herpes Genitalis / Q000188:drug therapy*; D018258:Herpesvirus 2, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood*; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir