Research Question
Can a vaginal microbicide applied before sexual intercourse reduce acquisition of HIV infection in women?
Primary Outcomes:
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Acquisition of HIV infection by the 12 month time point, confirmed in a central laboratory, in participants confirmed to be HIV negative at enrolment.
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A grade 3 (severe) or 4 (life-threatening) clinical or laboratory adverse event confirmed on examination or repeat testing respectively.
Secondary Outcomes:
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Acquisition of HIV infection by the 6 month time point, confirmed in a central laboratory, in participants confirmed to be HIV negative at enrolment.
- Acquisition of HIV infection by the 9 month time point, confirmed in a central laboratory, in participants confirmed to be HIV negative at enrolment.
- HSV-2 incidence rates by the 9 month time point in participants uninfected at enrolment.
- HSV-2 incidence rates by the 12 month time point in participants uninfected at enrolment.
- Cross-sectional prevalence of NG at 24 weeks, determined by a positive nucleic acid amplification assay.
- Cross-sectional prevalence of CT at 24 weeks, determined by a positive nucleic acid amplification assay.
- All systematically solicited genital adverse events.
- All clinical or laboratory adverse events.
Fit within AC portfolio
The MDP301 clinical trial forms part of the ‘Interventions to prevent transmission or acquisition of HIV infection’ portfolio.
Data source
The trial took place between October 2005 and August 2009 and enrolled 9404 women at 6 research centres in South Africa, Tanzania, Uganda and Zambia. The Africa Centre commenced screening in March 2006 and enrollment in April 2006. Participants remained in follow up at one of three research clinics for a total of 12 months, attending the clinics monthly. Africa Centre screened 1775 women and enrolled 1177 women in total. The main reason for ineligibility was HIV status which accounted for 28% of those screened.
Participants were originally randomised in approximately equal numbers to one of three study groups: PRO 2000 gel 0.5% dose, PRO 2000 gel 2% dose and placebo. In February 2008, an independent monitoring committee recommended that no more women should be allocated to 2% PRO 2000 gel as there was little chance that it would prove effective. The trial promptly stopped dispensing the 2% gel to all women including those already allocated to it but continued to follow up these women. All women enrolling subsequently were randomised to the other two study groups.
Participants were instructed to apply gel up to one hour before sexual intercourse. They were counselled on safe sexual behaviour and encouraged to use condoms, which were provided free of charge.
The trial was run by the Microbicides Development Programme, a not-for-profit partnership funded by the UK government through its Department for International Development and Medical Research Council.
The Africa Centre screened 1775 women and enrolled 1177 eligible women. Enrolled participants visited the research clinics every 4 weeks for a total of 52 weeks. Demographic, socio-economic, sexual behaviour and clinical data were collected at various time points. Sexual behaviour data from a sub-sample of participants was also collected using coital diaries. The data were locally managed using an Access application with a SQL Server database.
Findings
In the final analysis, PRO 2000/5 did not reduce the risk of infection with HIV or other STIs. There were no statistically significant differences in clinical outcomes between the gels.
Policy implications
Although the MDP 301 clinical trial demonstrated that PRO 2000 vaginal gel does not provide additional benefit to condoms and safe sex counselling, it demonstrated high levels of acceptability for the concept of using a vaginal gel for HIV prevention. It is unlikely that polyanion microbicides will be evaluated in the future, although the results of the MDP 301 trial will inform the future development of ARV based microbicide trial protocols.