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.

Figure 1.

Mean plasma HIV-1 RNA concentrations, by treatment arm (acyclovir dashed line, valacyclovir solid). Plasma viral load measurements were obtained weekly except for the day 1, 2, and 3 measurements at the beginning of each arm in order to assess early viral kinetics after drug initiation and day 3 in the washout period to assess viral rebound after drug discontinuation.

Figure 2.

Plasma HIV-1 concentrations for each study participant by treatment arm (acyclovir grey, valacyclovir black). The line represents the median and whiskers indicate the range. Undetectable levels were assigned values between 0 and the lower limit of quantification.