Valacyclovir Decreases Plasma HIV-1 RNA in HSV-2 Seronegative Individuals: A Randomized Placebo-Controlled Crossover Trial.
BACKGROUND
Acyclovir (ACV), a highly specific anti-herpetic drug, acts as a DNA chain terminator for several human herpesviruses (HHVs), including HHV-2 (HSV-2), a common human immunodeficiency virus (HIV)-1 co-pathogen. Several trials demonstrated that HSV-2 suppressive therapy using ACV or its prodrug valacyclovir (valACV) reduced plasma HIV-1 viral load (VL) in HIV-1/HSV-2 coinfected persons, and this was proposed to be due to a decrease in generalized immune activation. Recently, however, we found that ACV directly suppresses HIV-1 ex vivo in tissues free of HSV-2 but endogenously coinfected with other HHVs. Here, we asked whether valACV suppresses VL in HIV-1 infected HSV-2-seronegative persons.


METHODS
Eighteen HIV-1 infected HSV-2-seronegative individuals were randomly assigned in a double blind placebo-controlled, crossover trial. Eligible participants had CD4 cell counts of ≥500 cells/µL and were not taking antiretroviral therapy. Subjects in group A received 12 weeks of valACV 500 mg given twice daily by mouth followed by 2 weeks of a no treatment washout and then 12 weeks of placebo; subjects in group B received 12 weeks of placebo followed by 2 weeks of no treatment washout and then 12 weeks of valACV 500 mg twice daily.


RESULTS
HIV-1 VL in plasma of patients treated with valACV 500 mg twice daily for 12 weeks was reduced on average by 0.37 log10 copies/mL.


CONCLUSIONS
These data indicate that the effects of valACV on HIV-1 replication are not related to the suppression of HSV-2-mediated inflammation and are consistent with a direct effect of ACV on HIV-1 replication.
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Christophe
C
Vanpouille
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Andrea
A
Lisco
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Jean-Charles
JC
Grivel
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and VA Medical Center, Atlanta, Georgia.
Leda C
LC
Bassit
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and VA Medical Center, Atlanta, Georgia.
Robert C
RC
Kauffman
Asociación Civil Impacta Salud y Educación, Lima, Peru.
Jorge
J
Sanchez
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and VA Medical Center, Atlanta, Georgia.
Raymond F
RF
Schinazi
Division of Infectious Diseases and Center for AIDS Research, Case Western Reserve University and University Hospitals/Case Medical Center, Cleveland, Ohio.
Michael M
MM
Lederman
Division of Infectious Diseases and Center for AIDS Research, Case Western Reserve University and University Hospitals/Case Medical Center, Cleveland, Ohio.
Benigno
B
Rodriguez
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Leonid
L
Margolis
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000821:virology*; D012367:RNA, Viral / Q000097:blood*; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
D019380:Anti-HIV Agents; D010919:Placebos; D012367:RNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir
HIV-1; HSV-2; acyclovir; herpesvirus; reverse transcriptase inhibitor