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

• Published in: The Journal of infectious diseases Vol. 196; no. 10; pp. 1500 - 1508
• Main Authors: Zuckerman, Richard A., Lucchetti, Aldo, Whittington, William L. H., Sánchez, Jorge, Coombs, Robert W., Zuñiga, Rosario, Magaret, Amalia S., Wald, Anna, Corey, Lawrence, Celum, Connie
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.11.2007; University of Chicago Press
• Subjects: Acyclovir - administration & dosage; Acyclovir - analogs & derivatives; Acyclovir - therapeutic use; Administration, Oral; Adult; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; Biological and medical sciences; Blood plasma; Cross-Over Studies; DNA; DNA, Viral - analysis; Double-Blind Method; Fundamental and applied biological sciences. Psychology; Genitalia; Herpes Simplex - blood; Herpes Simplex - complications; Herpes Simplex - drug therapy; Herpes simplex virus 2; Herpesvirus 2, Human - genetics; HIV; HIV 1; HIV Infections - blood; HIV Infections - complications; HIV Infections - virology; HIV-1 - genetics; HIV/AIDS; Homosexuality, Male; Human herpesvirus 2; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Humans; Male; Microbiology; Miscellaneous; Placebos; Polymerase Chain Reaction; Rectum - virology; RNA; RNA, Viral - analysis; Simplexvirus; Treatment Outcome; Valine - administration & dosage; Valine - analogs & derivatives; Valine - therapeutic use; Viral Load; Virology; Human; Acyclic nucleoside; Purine nucleoside; HIV-1 virus; Herpesviridae; Suppression; Alphaherpesvirinae; Retroviridae; Valaciclovir; Prodrug; Lentivirus; Blood plasma; HIV-2 virus; Virus; Human herpesvirus 2; Nucleoside analog; Antiviral; Human herpesvirus 1; Herpesvirus hominis; Human immunodeficiency virus; DNA polymerase inhibitor
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/522523

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/μL 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) log10copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI, 0.23–0.42;P<.0001; 53% decrease) log10 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. Trial registration. ClinicalTrials.gov identifier: NCT00378976.