TAG 2010 Pipeline Report
The Immune-Based Therapies and Preventive Technologies Pipeline By Richard Jefferys Unlike the other pipelines discussed in this report, there are no approved immune-based therapies or biomedical preventive technologies for HIV—aside from antiretroviral therapy itself—(see 2010 Pipeline Summary) to offer a guidepost for product developers. For those attempting to navigate this uncharted terrain, 2009 proved to be another year of vertiginous ups and downs. In the realm of biomedical prevention, a microbicide candidate (PRO2000 gel) that came within a whisker of showing statistically significant protection in a phase IIb study (Abdool Karim 2009) failed to show any efficacy in a larger, definitive phase III trial (Chisembele 2010). PRO2000 gel was essentially the last in a class of broad-spectrum microbicide candidates and the focus has now shifted to products with more potent and specific anti-HIV effects. Meanwhile, a huge HIV vaccine trial that took place in Thailand involving two ancient candidates (ALVAC and AIDSVAX) surprised everyone by showing a meager (31.2%) but just about statistically significant degree of protection (Rerks-Ngarm 2009). Despite the size of the trial, however, there were relatively few HIV infection endpoints and the confidence intervals—a statistical measure of the uncertainty associated with a result—were vast, raising the specter that the findings may be as illusory as those of the phase IIb PRO2000 gel trial. Nevertheless, after the paucity of good news in HIV vaccine research, and despite the possibility of a statistical fluke, the Thai trial results have been widely hailed as historic. Plans are now afoot to try and reproduce and improve upon them with similar regimens. Results from the first efficacy trials of preexposure prophylaxis (PrEP) are due to become available later this year, after this report is printed. The antiretrovirals being studied for PrEP are tenofovir and the combination of tenofovir and emtricitabine in a single pill (Truvada). Several other agents are under consideration but, unsurprisingly, PrEP research is currently in a holding pattern awaiting the crucial first efficacy data. Several small studies are evaluating the safety and acceptability of intermittent rather than continuous PrEP, but as yet no efficacy studies are planned.
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