Earlier this year at the Conference on Retroviruses & Opportunistic Infections, Salim Abdool Karim presented data suggesting that a vaginally applied microbicide gel called PRO 2000 might offer some protection against HIV infection in high-risk women. The results were not statistically significant but represented a strong trend, and the suggested effect was a slight 30% reduction in risk of acquisition of the virus. Some commentators at the meeting noted that because this study had two separate control arms (a placebo gel and no gel), comparing the total number of control participants from both of these arms with the group that received PRO 2000 would render the result statistically significant. To his credit, Karim emphasized that such an analysis was not a pre-specified part of the protocol and was therefore inappropriate. He also pointed out that there was a larger, ongoing phase III study of PRO 2000 involving over 9,000 women that would provide a definitive answer as to the product’s efficacy.
The results from this trial, called MDP-301 and run by the UK Medical Research Council in close collaboration with Imperial College in London and investigators in four African countries, were announced today. Disappointingly, the hint of efficacy seen in the smaller phase IIb was not duplicated: there were 130 HIV infections among the 3,156 women that received PRO 2000 gel, and 123 infections in the group of 3,112 women that received placebo gel.
The first news story reporting the result appeared in the Times of London yesterday and broke the embargo on the MRC releases by several hours; it was subsequently taken offline before being reinstated earlier today. The article dramatically - but erroneously - characterizes the PRO 2000 result as “a significant setback.” The whole purpose of large phase III efficacy trials is to definitively answer the question of whether an intervention works and, quite often, they don’t. In the case of PRO 2000, the microbicide is one of the last in a pipeline of products with relatively limited direct antiretroviral activity and, over the past several years, there has been increasing recognition in the field that more specific products are needed. Several such antiretroviral microbicides, such as the gel form of the drug tenofovir (Viread) are now in trials.
A number of informational resources on the MDP-301 trial are available on the web:
Global Campaign for Microbicides
Disappointment as microbicide fails to protect against HIV
By Keith Alcorn (Aidsmap)
The Global Campaign for Microbicides is also hosting a tele-briefing for advocates tomorrow (Tuesday, December 15) at 9am EST to discuss the findings from MDP 301. Speakers on the call include the principal investigator for MDP 301, Sheena McCormack and the site investigator from the Africa Centre in South Africa, Mitzy Gafos. To participate, pre-registration is required at: https://cc.readytalk.com/r/usngsqfcqq0e
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