Phase II/IIb Safety and Effectiveness Study of the Vaginal Microbicides BufferGel and 0.5% PRO2000/5 Gel (P) for the Prevention of HIV Infection in Women
What is HPTN 035?
Read about the study and its results in these documents:
HPTN 035 was a multi-center clinical research study that evaluated the safety and effectiveness of two candidate vaginal microbicides, BufferGel and 0.5% PRO 2000/5 Gel (P), for the prevention of HIV infection in women.
The study was conducted between February 2005 and September 2008 through a partnership involving US and African researchers and the communities in which the study was conducted. The study research teams now collaborate in the Microbicide Trials Network (MTN). Prior to 2006, the study was conducted by the HPTN, from which the study gets its name.
HPTN 035 was a Phase II/IIb study designed to determine whether BufferGel or 0.5% PRO 2000 Gel had sufficient promise to be considered for testing in a larger Phase III study. To evaluate their safety and effectiveness, both candidate products were compared to a placebo gel and to no gel. Study participants were randomly assigned to one of four groups: BufferGel, PRO 2000 Gel, placebo gel, no gel. The Phase II portion of the study involved intensive safety evaluations among the first 799 women enrolled in the study. The Phase IIb portion involved the first 799 women and an additional 2300 women.
Protocol Status: Concluded
Study Purpose: To determine the safety and effectiveness of two candidate vaginal microbicides: BufferGel and 0.5% PRO 2000 Gel (P).
Study Design: Phase II/IIb, four-arm, multisite, randomized controlled trial comparing BufferGel and 0.5% PRO 2000/5 Gel (P) with a placebo gel and with no gel. The three study gel arms were double-blinded. The Phase II portion of the study was conducted as an uninterrupted lead-in to the Phase IIb portion. Each study participant completed approximately 12-30 months of follow-up (20 monts on average).
Study Population: Sexually active HIV-uninfected women from the following study sites: Blantyre, Malawi; Lilongwe, Malawi;; Durban, South Africa; Hlabisa, South Africa; Lusaka, Zambia; Harare, Zimbabwe; Philadelphia, PA, USA
Study Size: 3099 women
Study Duration: February 2005 through September 2008
Treatment Regimen: Participants assigned to the three study gel groups were instructed to apply a single dose of their randomly assigned product − BufferGel, 0.5% PRO 2000/5 Gel (P), or placebo gel − intravaginally up to 60 minutes before each act of vaginal intercourse using single-use, pre-filled applicators. Participants in all four groups received ongoing HIV risk reduction counseling, condoms, and diagnosis and treatment of sexually transmitted diseases.
Primary Objectives: To evaluate the safety of BufferGel and 0.5% PRO2000/5 Gel (P) when applied intravaginally by women at risk for sexually-transmitted HIV infection. To estimate the effectiveness of BufferGel and 0.5% PRO 2000/5 Gel (P) in preventing HIV infection among at-risk women.
Secondary Objectives: To estimate the effectiveness of BufferGel and 0.5% PRO 2000/5 Gel (P) in preventing the following among women at risk for sexually-transmitted HIV infection: bacterial vaginosis, chlamydia infection, genital ulcer disease, gonorrhea infection, herpes simplex virus-2 infection, pregnancy, syphilis infection, trichomoniasis. To assess the acceptability of BufferGel and 0.5% PRO 2000 Gel (P) for use as a vaginal microbicide.
HPTN 035 Publications
Macqueen KM, Namey E, Chilongozi DA, Mtweve SP, Mlingo M, Morar N, Reid C, Ristow A, Sahay S, HPTN 035 Standard of Care Assessment Team. Community perspectives on care options for HIV prevention trial participants. AIDS Care. 2007, 19: 554-60 PMID:17453597.
Abdool Karim SS, Richardson BA, Ramjee G, Hoffman IF, Chirenje ZM, Taha T, Kapina M, Maslankowski L, Coletti A, Profy A, Moench TR, Piwowar-Manning E, Mâsse B, Hillier SL, Soto-Torres L; HIV Prevention Trials Network (HPTN) 035 Study Team. Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS. 2011, 25: 957-99 PMCID: 3063640.
Schreiber CA, Whittington S, Cen L, Maslankowski L. Good intentions: risk factors for unintended pregnancies in the US cohort of a microbicide trial. Contraception. 2011, 83: 74-81 PMID:21134507.
Dai JY, Gilbert PB, Mâsse BR. Partially hidden Markov model for time-varying principal stratification in HIV prevention trials. J Am Stat Assoc. 2012, 107: 52-65 PMCID: 3649016.
Woodsong C, Alleman P, Musara P, Chandipwisa A, Chirenje M, Martinson F, Hoffman I. Preventive misconception as a motivation for participation and adherence in microbicide trials: evidence from female participants and male partners in Malawi and Zimbabwe. AIDS Behav. 2012, 16: 785-90 PMCID: 3658446.
Gorbach PM, Mensch BS, Husnik M, Coly A, Mâsse B, Makanani B, Nkhoma C, Chinula L, Tembo T, Mierzwa S, Reynolds K, Hurst S, Coletti A, Forsyth A. Effect of computer-assisted interviewing on self-reported sexual behavior data in a microbicide clinical trial. AIDS Behav. 2013, 17: 790-800 PMCID: 3550005.
Richardson BA, Kelly C, Ramjee G, Fleming T, Makanani B, Roberts S, Musara P, Mkandawire N, Moench T, Coletti A, Soto-Torres L, Karim SA; HPTN 035 Study Team. Appropriateness of hydroxyethylcellulose gel as a placebo control in vaginal microbicide trials: a comparison of the two control arms of HPTN 035. J Acquir Immune Defic Syndr. 2013, 69: 120-5 PMCID: 3625489.
Gorbach PM, Kelly CW, Borgerding JA, Ramjee G, Tembo T, Kumwenda N, Musara P, Roberts S, Maslankowski L. Effects of partnership change on microbicide gel adherence in a clinical trial (HPTN 035). AIDS Behav. 2014, 18: 855-61 PMCID: 3988261.
Guffey MB, Richardson B, Husnik M, Makanani B, Chilongozi D, Yu E, Ramjee G, Mgodi N, Gomez K, Hillier SL, Karim SA; HIV Prevention Trials Network (HPTN) 035 Study Team. HPTN 035 phase II/IIb randomised safety and effectiveness study of the vaginal microbicides BufferGel and 0.5% PRO 2000 for the prevention of sexually transmitted infections in women. Sex Transm Infect. 2014, 90: 363-9 PMCID in process.
Zhang J, Brown ER. Estimating the effectiveness in HIV prevention trials by incorporating the exposure process: Application to HPTN 035 data. Biometrics. 2014, May 20: ahead of print. PMCID in process.