Phase II Expanded Safety and Acceptability Study of the Vaginal Microbicide 1% Tenofovir Gel
What is HPTN 059?
Evaluating the safety of new candidate microbicides is the first step in the critical path to effectiveness trials. While the condom is an effective tool in preventing the sexual transmission of HIV, its use in many African and Asian countries is severely hampered by deeply rooted cultural and social barriers. Thus, efforts to find alternative preventive interventions, such as vaginal microbicides, to slow the rapid spread of heterosexual HIV infection are urgently needed. Effectiveness trials of vaginal microbicides conducted to date have all involved products containing nonoxynol-9 (N-9), a marketed spermicide that acts as a surfactant, destroying cellular and microbial membranes. Several formulations of nonoxynol-9 (N-9) have been tested at various concentrations in humans for safety and effectiveness. Four randomized controlled trials have shown that use of N-9 does not protect against HIV infection. Higher doses and more frequent use of N-9 have been linked to increased findings of genital lesions. Women-controlled methods of HIV prevention are urgently needed throughout the world to help control the spread of HIV infection.
HPTN 059, a multi-center phase II study, was designed to determine the safety of tenofovir 1% gel as a vaginal microbicide over 24 weeks, and to gain additional information regarding product's acceptability. As a four arm, randomized controlled trial, it compared two frequencies of use (daily and coitally dependent), and corresponding placebo gel arms. Half of the participants across cohorts took part in the "standard safety" study and had pelvic exams without colposcopy. The other half of the participants took part in an "expanded safety study" and had pelvic exams with colposcopy and specimen collection for cytokine testing. All participants were counseled to use, and were provided with, male latex condoms. Participants were also counseled to use the study products daily or with each act of vaginal intercourse.
Tenofovir is an adenosine nucleoside monophosphate (nucleotide) belonging to the class of acyclic phosphonomethylether nucleosides, and is currently approved as antiretroviral therapy in the oral form. In nonclinical studies the 1% concentration of gel prevented SIV infection in rhesus macaques, and was well tolerated in rabbit vaginal toxicity tests. Preliminary results from the HPTN 050 study have shown tenofovir gel to be safe and acceptable.
Protocol Status: Concluded
Study Purpose: To assess the safety of tenofovir gel for vaginal use in HIV-uninfected women versus a placebo gel.
Study Design: Phase II four arm, three site randomized, controlled trial comparing tenofovir 1 % vaginal gel used once daily and tenofovir 1% vaginal gel used prior to intercourse, to a placebo gel study, with 6 months tenofovir gel exposure and follow-up. Participants who are HBV positive will return to site at visits Weeks, 28, 32, and 36 (post product use). Participants in all four arms will receive ongoing condom counseling and free condoms. The study will be conducted at thee sites; Pune, India; Alabama, Birmingham, USA; New York, USA.
Study Population: The proposed study population will consist of up to 200 sexually active, HIV-uninfected women between the ages of 18 and 50, but not menopausal or post menopausal.
Study Size: The Pune, UAB, and New York sites will enroll a total of 200 women.
Study Duration: Six months of tenofovir gel exposure and six months follow-up. HBV positive participants will be followed at 4, 8 and 12 weeks post exposure to monitor for rebound. Consequently study duration will be six to nine months.
Treatment Regimen: Once enrolled, participants will be randomized into either the once daily or the coitally dependent group, and will receive either tenofovir or placebo gel. Participants will receive single use unit dose tube and single use applicator to be filled by the participant to be used either once daily or with each act of intercourse. Throughout the study, participants will receive ongoing condom counseling and free condoms.
Primary Objectives: To assess the safety of tenofovir gel for vaginal use in HIV-uninfected women versus a placebo gel.
Secondary Objectives: To assess the acceptability of and adherence to, two regimens of tenofovir gel in women. To assess participant study burden. Exploratory Objectives To measure vaginal flora characteristics, and to descriptively examine changes in these characteristics over the course of prolonged tenofovir vaginal gel use To assess the effects of tenofovir gel on cytokine and chemokine expression in cervical secretions To evaluate the association between cytokine and chemokine expression To correlate cytokine expression with colposcopic evidence of inflammation, epithelial disruption and genital symptoms