HIV Prevention Research Programme / Microbicide Effectiveness Trial

Lead Research Organisation: MRC/UVRI Uganda Research Unit on AIDS

Abstract

Women are more vulnerable to HIV infection through heterosexual transmission than men because of biological reasons and because of socio-economic and cultural factors that make negotiation of safer sexual practices difficult. Vaginal microbicides may be effective in preventing the transmission of HIV infection to a women from an infected partner. Vaginal microbicides are chemical substances that may work e.g. by blocking HIV from entering the wall of the vagina or the uterus or by killing the virus. There are a variety of possible microbicide products under investigation.|A large scale trial has been conducted from 2005 2009 by the international Microbicides Development Programme, a collaboration of 6 African research institutions, the MRC Clinical Trials Unit London and Imperial College London. The product to be tested was PRO 2000/5, which had been shown to be effective against HIV when tested in the laboratory, and shown to be safe in several smaller studies. The trial aimed to establish whether this product is effective in preventing HIV infection among HIV-negative women. The trial found that the product was safe to use but was ineffective in providing protection against HIV infection. This result was very disappointing. However it provided conclusive evidence that the type of vaginal microbicide product investigated does not protect HIV negative women against HIV acquisition. Research continues to find a product that is both safe and effective.

Technical Summary

Objective: To evaluate the efficacy and safety of two concentrations of a vaginal microbicide gel (0.5% and 2% PRO 2000/5) in preventing vaginally acquired HIV infection.|Methods: This trial (MDP-301) was a multi-centre randomised placebo controlled trial involving the MRC/UVRI Uganda Unit and five partner institutions in Tanzania, Zambia and South Africa. The study was coordinated by the MRC Clinical Trials Unit in London and Imperial College London. It was part of the Microbicides Development Programme (MDP) which was funded by the Department for International Development (DFID) and the MRC. The product under investigation was an aqueous gel consisting of a naphthalene sulphonic acid polymer, provided by Indevus Pharmaceuticals Inc. (USA). Its principle safety and acceptability had been evaluated earlier. Primary outcome measures comprised the acquisition of new HIV infection and the occurrence of adverse events. The trial involved 9,385 women enrolled at the six African researh centres. The MRC/UVRI Uganda Research Unit on AIDS enrolled women into the trial who lived in a HIV sero-discordant couple relationship. |The trial began in 2005 and was completed by the end of 2009. The results have recently been communicated. |(see http://www.mdp.mrc.ac.uk; 17th Conference on Retroviruses and Opportunistic Infections 2010, late breaker abstract 87LB)|Results: The trial found that the risk of HIV infection in women who were supplied with PRO 2000 gel was not significantly different than in women supplied with placebo gel. Although ineffective in providing protection, PRO 2000 gel itself was safe to use. This study outcome, whilst disappointing, provided definite evidence that the poly-anion class of vaginal microbicides does not protect HIV negative women against HIV acquisition.

Publications

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Excler JL (2011) AIDS vaccines and preexposure prophylaxis: is synergy possible? in AIDS research and human retroviruses

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Kamali A (2010) What is new in HIV/AIDS research in developing countries? in Tropical medicine & international health : TM & IH

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Namakoola I (2010) Use of nail and oral pigmentation to determine ART eligibility among HIV-infected Ugandan adults. in Tropical medicine & international health : TM & IH

 
Description Member of the National Expert Think Tank of the HIV Prevention
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact To develop a sound and evidence-based HIV Prevention Strategy for Uganda closely linked to the Uganda National Multisectoral HIV/AIDS Strategic Plan.
 
Description IAVI Clinical Trial and Laboratory Program for 2010
Amount £827,000 (GBP)
Organisation International AIDS Vaccine Initiative (IAVI) 
Sector Charity/Non Profit
Country Global
Start 06/2004 
End 06/2016
 
Description International AIDS Vaccine Initiative (IAVI) Clinical Trial and Laboratory HIV Vaccine Program 2011
Amount £910,000 (GBP)
Organisation International AIDS Vaccine Initiative (IAVI) 
Sector Charity/Non Profit
Country Global
Start 01/2011 
End 12/2011
 
Description Strengthening of long term clinical and laboratory research capacity, cohort development, and collection of epidemiological and social science baseline data in Uganda and Malawi to prepare for future HIV vaccine trials.
Amount £2,335,025 (GBP)
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country European Union (EU)
Start 06/2008 
End 05/2010
 
Description EDCTP 
Organisation Sixth Framework Programme (FP6)
Department European and Developing Countries Clinical Trials Partnership
Country European Union (EU) 
Sector Public 
PI Contribution Understanding HIV transmission patterns in fishing communities and its contribution to the HIV epidemic trends in Uganda
Collaborator Contribution Strengthening of long term clinical and laboratory research capacity, cohort development, and collection of epidemiological and social science baseline data in Uganda and Malawi to prepare for future HIV vaccine trials.
Impact A number of scientific presentations at national and international conferences and publications in peer reviwed journals.
Start Year 2008
 
Description International AIDS Vaccine Initiative (IAVI) 
Organisation International AIDS Vaccine Initiative (IAVI)
Country Global 
Sector Charity/Non Profit 
PI Contribution Developed an HIV high risk cohort in preparation for HIV vaccine trials. Conducted HIV prevalence and incidence, acute HIV infection studies which are relevant to future HIV vaccine studies and development. Condcted a pilot study of Pre-Exposure Prophylaxis (PrEP) to evaluate safety, acceptability, and adherence in at-risk populations in Uganda, Africa. The study is just been completed. We are starting shortly a Phase I double-blinded, placebo-controlled, randomized trial in HIV uninfected,healthy adult volunteers evaluating the safety and immunogenicity of F4co adjuvanted with AS01B or AS01E administeredwith Ad35-GRIN
Collaborator Contribution Training and Infrastructure development
Impact Clinical and cell laboratories have been established at the field station, which have been acredited. Staff been trained in GCP/GCLP standards. A vaccine pharmacy has been established to support the forthcoming phase I HIV vaccine trial. The collaboration is multidisciplinary involving Basic Science, Epidemiology and Clinical Medicine.
 
Description Microbicide Development Programme (MDP) 
Organisation Medical Research Council (MRC)
Department MRC Clinical Trials Unit
Country United Kingdom 
Sector Public 
PI Contribution We participated and contributed to the design, conduct and data management of the trial. Contributed 840 women to the overall sample size.
Collaborator Contribution Training and Insfrastructure development
Impact Provided HIV counselling and testing, STI screening and treatment to all particapnts. Presented key findings at international conferences. Final results have just been released and publication plan is underway.
 
Description HIV Care support organisations, CAB members and wider community 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Continous dissemination to the wider community, Community Advisory Board members, and to our non-acedmic partners such as TASO and other HIV care support organisations. Several hundreds of people reached.

Better support to our research activities, and high retention in our follow up of cohorts.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Political leaders 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact On a regular basis we organise meetings with the local political leadership to up date them on progress of our activities. At national level meetings are held with parliamentarians.

Dissemination and mobilisation of our resarch activities in their respective constituencies.
Year(s) Of Engagement Activity 2008,2009,2010,2015,2016
 
Description Various Press (TV, Radio, and Print) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Held a press conference to discuss the findings of the IPM phase III trial. Attracted several journalists from many press houses. Continuous update of our research activities to the media.

Information disseminated through the print and radio/TV media. Final Press conference was attended by senior Ugandan Ministry of health officials including the Minister of health.
Year(s) Of Engagement Activity 2008,2009,2010,2013,2014