HPTN 039

A Phase III, randomized, double-blind, placebo-controlled trial of acyclovir for the reduction of HIV acquisition among high risk HSV-2 seropositive, HIV-seronegative individuals

Study Summary

What was HPTN 039?

A Phase III, multi-site, randomized, double-blind, placebo-controlled 2-arm trial of daily acyclovir to determine the efficacy of twice daily acyclovir in preventing HIV infection among high risk HIV-negative, HSV-2 positive women and men who have sex with men (WSM, MSM)

Who participated in the study?

High risk HIV-uninfected, HSV-2 positive WSM and MSM

What happened during the study?

Study participants were randomized to one of two arms: Acyclovir 400 mg po bid and Matching placebo po bid

Results

In the final analysis of the study, which officially ended in November 2007, researchers found no evidence that twice-daily acyclovir prevents HIV infection among HSV-2 infected women and men who have sex with men. Specifically, there was a 3.9 percent HIV incidence rate (75 cases) among those participants who received acyclovir, while there was a 3.3 percent HIV incidence rate (64 cases) among those who received placebo. There was no statistically significant difference in HIV rates between those participants who received acyclovir and those who received placebo. Additionally, the study provided evidence that acyclovir reduces the occurrence of genital ulcers in HSV-2-infected individuals. The participants who received acyclovir experienced a 37 percent reduction in genital ulcer incidence.

Why was this study important?

The presence of genital ulcers has been suggested as a potential risk factor for HIV acquisition since the start of the HIV epidemic. Although observational data had indicated an increased risk of HIV infection among HSV-2 seropositive persons, a reduction in HIV infection due to daily HSV-2 suppression had not yet been tested or demonstrated. Thus, this study was one of the first to examine HSV-2's role in HIV acquisition.

Study Details

Protocol Status: Concluded
Study Purpose:

To determine the efficacy of twice daily acyclovir in preventing HIV infection among high risk HIV-negative, HSV-2 positive women and men who have sex with men (WSM, MSM)

Study Design:

Phase III, multi-site, randomized, double-blind, placebo-controlled 2-arm trial of daily acyclovir

Study Population:

High risk HIV-uninfected, HSV-2 positive WSM and MSM

Study Size:

Total of 2820 to 3012 participants

Study Duration:

Approximately 36 months total. Enrollment: 18 months. Follow-up: 18 months per participant

Treatment Regimen:

Study participants will be randomized to one of two arms:
Acyclovir 400 mg po bid
Matching placebo po bid

Primary Objectives:

To measure the efficacy of twice daily acyclovir suppressive therapy in preventing HIV infection among HSV-2 seropositive, HIV-negative WSM and MSM at high risk for HIV infection.

Secondary Objectives:

To determine the effect of twice daily acyclovir suppressive therapy on reducing the occurrence and frequency of genital ulcers among HIV-negative HSV-2 seropositive persons.
To assess adherence with twice daily acyclovir suppressive therapy among HIV-negative HSV-2 seropositive individuals.