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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

039 Quick Links • HPTN 039 Study summary • HPTN 039 Background • HPTN 039 Q&A • HPTN 039 Data Communiqué #4 • HPTN 039 Data Communiqué #3 • HPTN 039 Data Communiqué #2 • HPTN 039 Data Communiqué #1 • HPTN 039 SSP Manual 17 September 2004 (PDF) • HPTN 039 v 3.0 Protocol & successive docs (PDF) • Amendment 2 Summary • HPTN 039 v 2.0 Protocol & successive docs (PDF) • Amendment 1 Summary • HPTN 039 v 1.0 Protocol (PDF) • HPTN 039 Meetings & Presentations • HPTN 039-01-Ancillary • HPTN 039 Alias Lists

What is HPTN 039?

The presence of genital ulcers has been suggested as a potential risk factor for HIV acquisition since the start of the HIV epidemic. Numerous epidemiologic studies have supported the association of genital ulcers in general, and genital herpes in particular, with acquisition of HIV infection. Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcers worldwide. This has been well documented in developed countries and has recently been shown in the developing world. HPTN 039 was a double-blind, placebo-controlled intervention trial of daily antiviral HSV-2 suppressive therapy for HIV prevention with a reasonable risk/benefit profile for participants. Although observational data indicate an increased risk of HIV infection among HSV-2 seropositive persons, a reduction in HIV infection due to daily HSV-2 suppression has not yet been tested or demonstrated. Participants in the placebo arm were provided with more than the standard of care for many U.S. settings, by provision of episodic antiviral treatment for symptomatic herpes outbreaks.

HPTN 039 was a Phase III, multi-site, randomized, double-blind, placebo-controlled trial that enrolled a total of 3,277 high-risk, HIV-negative, HSV-2 seropositive WSM and MSM over an accrual period of approximately 18 months. WSM were enrolled at study sites in Lusaka, Zambia, Johannesburg, South Africa, and Harare, Zimbabwe. MSM were enrolled at study sites in Lima, Iquitos, and Pucallpa, Peru; Seattle, WA, USA; New York City; NY, USA; and San Francisco, CA, USA.  The study was the largest clinical trial to date to examine herpes suppression as a possible means of reducing the risk of HIV transmission.

Study 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.

Additional Information on the Study Results:

• NIAID Press Release
• Principal Investigator's Presentation at CROI 2008
• Lancet Article (June 21 2008)

Protocol Status: Participants Off Study & Primary Analysis Complete

Study Summary

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.

SDMC Protocol Specialist: Heather Hildebrant get info

Protocol Co-Chair: Anna Wald get info

Protocol Chair: Connie Celum get info

DAIDS Medical Officer: Arnaldo Quinones get info

DAIDS Medical Officer: Sheryl Zwerski get info

CORE Protocol Specialist: Sam Griffith get info

CORE Protocol Specialist: Scott Rose get info

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