Title: Prevention Programme - Microbicides
Funder: Medical Research Council

Abstract: The focus of this programme is to develop female controlled methods to prevent HIV which are safe, effective and affordable. |In the absence of an effective vaccine to prevent the spread of HIV-infection and the continuing HIV pandemic, which is particularly devastating in sub-Saharan Africa there is an urgent need to develop alternative methods of prevention. Women in sub-Saharan Africa are particularly vulnerable being unable in most instances to negotiate the use of condoms with their partners. |A central objective is the development and clinical assessment of candidate microbicides for the prevention of vaginally acquired HIV infection. The CTU is jointly co-ordinating the multi-disciplinary Microbicides Development Programme with Imperial College at St Marys Hospital, London.||The initial work focused on testing the safety of 2 candidate microbicides both in Europe (Antwerp and the UK) and in Africa (Uganda). In parallel to these trials, Feasibility studies were conducted in 6 African sites, to inform the design and size of a Phase 3 trial to assess two active products. A short Pilot study using placebo gel was conducted to validate the procedures planned for the main trial, and a final evaluation of the pre-clinical and clinical data was performed in August 2004 to select the product and concentration. A large Phase 3 trial of low and hig dose PRO 2000/5 vaginal gel began recruiting in 2005. CTU coordinated the development of the protocol, case record forms, database, monitoring, analyses and oversight (Trial Management Group, Trial Steering Committee and Data and Safety Monitoring Committee meetings).||Between October 2005 and August 2008 9385 women were enrolled from the following sub-Saharan African sites, in South Africa (Johannesburg, Soweto and Orange Farm, Durban, Tongaat, Verulam and Isipingo, Africa Centre), Tanzania (Mwanza), Uganda (Masaka), and Zambia (Mazabuka). Women were followed for at least 12 months (up to 24months in Uganda) and were asked to insert the gel pre-sex.||The trial assessed two doses of PRO2000/5 (2% and 0.5%) each in comparison with a placebo. In February 2008 the 2% gel was discontinued on the recommendation of the Independent Data Monitoring Committee as there was no more than a small chance of demonstrating benefit according to the original statistical plan.||Recruitment closed on the 15th of August 2008 and follow up will continue until August 2009. The study database was locked on the 1st November 2009 and the results were reviewed by the Senior Investigators, Trial Steering and Independent Data Monitoring Committees as well as two independent referees appointed by MRC prior to release of the result in December 2009. Unfortunately neither 0.5% nor 2% PRO 2000/5 reduced the incidence of HIV when compared to placebo gel.||The next scientific questions are focused around the more potent anti-retroviral microbicides, and MDP is preparing for the results of the CAPRISA 004 trial of tenofovir 1% vaginal gel which will report in July 2010. In anticipation of significant but moderate protection we are conducting a further pilot of daily placebo gel, the Top-Up study in 5 sub-Saharan countries: Uganda (Masaka), Tanzania (Mwanza), South Africa (Durban), and Zambia (Mazabuka) all of which participated in the Phase 3 trial, plus Mozambique (Maputo and Manhica) where they have successfully completed a Feasibility study. Three methods of collecting in the used applicators are being explored: daily, weekly and every 4 weeks at the clinic visits. Top-Up has been enrolling since June 2010 and is expected to report early 2011.


Research activity codes: 5.1 PHARMACEUTICALS;6.1 PHARMACEUTICALS
Health categories: INFECTION