In collaboration with the Tanzania National Institute for Medical Research (NIMR) and London School of Hygiene and Tropical Medicine (LSHTM)

An international multi-centre, randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of 0.5% and 2% PRO 2000/5 gels for prevention of vaginally acquired HIV infection

Principal Investigators: Richard Hayes, Saidi Kapiga

Chief Investigators of the multi-centre trial: Charles Lacey (University of York, UK), Sheena McCormack (MRC Clinical Trials Unit)

Co-Investigators: Caroline Allen (LSHTM), Celia Barberousse (LSHTM), Claire Cook (LSHTM), John Changalucha (NIMR), Sheila Harvey (LSHTM), Shelley Lees (LSHTM), Joseph Masanja (AMREF), Claire Moffat (AMREF/LSHTM), David Ross (LSHTM), Andrew Vallely (AMREF/LSHTM), Deborah Watson-Jones (LSHTM)

Funding: DFID and MRC to the Microbicides Development Programme (MDP), a consortium of UK and African institutions

Bar facility in Mwanza City.

Background: The Microbicides Development Programme (MDP), a not-for-profit partnership of African and European research institutions, conducted a phase III clinical trial (MDP 301) to test the vaginal microbicide gel PRO 2000 in protecting women against HIV. The trial was conducted between 2005 and 2009 at six centres in four African countries. In Tanzania, this trial was conducted in Mwanza as a collaboration between the African Medical and Research Foundation (AMREF), the London School of Hygiene & Tropical Medicine (LSHTM), the National Institute for Medical Research (NIMR) and MITU.

Objectives and study design: The primary objective of this trial was to assess the efficacy and safety of 0.5% and 2% PRO 2000/5 Gel compared to placebo gel in preventing vaginally acquired HIV infection before or at 12-months. Eligible women were randomly allocated to one of the three study arms - PRO 2000 0.5%, PRO 2000 2% or placebo gel. They were instructed to insert one dose of the gel within one hour before each vaginal sex act. In February 2008, the Independent Data Monitoring Committee recommended that allocation of women to the PRO 2000 2% arm should stop as there was little chance that it would prove effective. During follow up, women were asked to attend the trial clinic every four weeks for 52 weeks.

Community liaison activities.

Main study findings: Of the 15818 women at high-risk of HIV infection who were screened across the six centres, 9385 were enrolled into the trial. In Mwanza, 1146 out of 2183 women screened were enrolled in the trial. Overall reported use of condoms rose from 57% to 70% during the course of the trial and was similar in the two groups, namely the PRO 2000 0.5% and placebo gel. Reported use of gel was high throughout the trial - around 90% in both study groups. In Mwanza, condom use was low and remained at around 30% throughout the trial. However, there was high reported use of the gel, around 95%. Social science data indicate that women and their partners liked using the gel. There was no significant difference in the rate of acquisition of HIV infection between PRO 2000 0.5% gel and placebo gel – hazard ratio 1.05, 95% confidence interval (CI) 0.82 – 1.34 (censored for pregnancy). There was also no significant difference in safety markers between the PRO 2000 gels and placebo gel.

Conclusions: Although safe, 0.5% PRO 2000 and 2% PRO 2000 are not efficacious against vaginal HIV-1 transmission and are not indicated for this use.