1Infectious Diseases Institute, Makerere University, Kampala, Uganda2Departments of Global Health3Medicine4Epidemiology, University of Washington, Seattle5Department of Obstetrics and Gynecology, Kenyatta National Hospital, Nairobi6Institute of Tropical Medicine and Infectious Diseases, Jomo Kenyatta University, Nairobi, Kenya
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(See the editorial commentary by Tanton et al, on pages 1822–6.)Background. Standard-dose HSV-2 suppressive therapy (acyclovir 400 mg twice daily) reduces plasma HIV-1 levels by 0.25–0.50 log10 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 log10 copies/mL, an average difference of 0.62 log10 copies/mL (95% confidence interval [CI]: −0.68, −0.55; P < .001), a 76% decrease. Valacyclovir resulted in a 1.23 log10 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 log10 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.