PRO 2000 microbicide gel does not pan out

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. [1]

The results were not statistically significant but represented a trend, suggesting a 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 emphasised 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 on 14 December. 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 newspaper (UK edition) the day before and broke the embargo on the MRC releases by several hours; it was subsequently taken offline before being reinstated. The article dramatically – but erroneously – characterises 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.

Background materials from the trials sponsor, the Microbicide Development Programme of the UK Medical Research Council:
http://www.mdp.mrc.ac.uk