"Failure informs future success." The HIV vaccine and microbicide researchers who took to the stage on Monday to discuss the future of these experimental HIV prevention technologies repeated this mantra throughout the symposium.
The halted STEP vaccine study perhaps best illustrates this point. Last year an interim analysis showed Merck's Ad-5 vaccine was ineffective and may have even enhanced risk of HIV infection. But Susan Buchbinder, a STEP investigator, emphasized the valuable lessons learned from the study: the utility of the test-of-concept trial (Phase IIb) to give us quick answers; that we must recalibrate the non-human primate model to better understand its applicability; and a wealth of data was mined, even leads on potential immune correlates. Predicting a positive immune response remains an important yet elusive goal in testing HIV vaccines.
The panelists emphasized the need
for truly novel ideas in moving forward in vaccine discovery, some bordering
on weird science like reducing, not enhancing an immune response, promoting
more mutations, and using replicating viral vectors for vaccine delivery.
The Bill & Melinda Gates Foundation, characteristically leading
the charge, this year implemented its Grand Challenges Explorations,
a $100 million initiative to encourage bold and unconventional science.
Although the microbicide research field is no stranger to setbacks, Zeda Rosenberg, from the International Partnership for Microbicides, spoke of the optimism around ARV-containing candidates. This new generation of microbicides is thought to be more potent than its predecessor because of its known anti-HIV properties. Some microbicides contain combination ARVs, expected to offer multi-mechanism protection.
Learning from past trials, or what some would loosely call "failures," consistent use of the microbicide in the intervention arm has proved to be a challenge. Responding to this finding, microbicides are being designed for longer protection to make adherence easier. Prospects include a once-daily or even a 30-day microbicide delivered via a vaginal ring.
A robust pipeline to hedge against failures is needed in both vaccine and microbicide pursuits, panelists agreed. "Nine out of 10 drugs or vaccines end with failures," said Tachi Yamada of the Gates Foundation. "Success is about long-term investment, not about today or tomorrow, but sometime in our lifetime."
