Closer to a Cure?

With two different foundations making announcements just a few days apart that they would be awarding multimillion-dollar grants to boost efforts to defeat HIV, the world of research began to look more hopeful and feel more energized, especially when the elusive c word'cure'was actually used. In late June the Bill and Melinda Gates Foundation pledged $287 million over the next five years for 16 research teams to study HIV vaccine development. The announcement came on the heels of news that investor Warren Buffett would donate $31 billion of his fortune to the Gates Foundation, thus doubling its current endowment. Less than a week after the Gates Foundation news, the American Foundation for AIDS Research announced a wave of grants for scientists to pursue what many have concluded is the stuff of mere fantasy: a cure for HIV. The $1.5 million divided among 12 research teams may be minute in comparison to the more than quarter billion coming from the Gateses, but Rowena Johnston, amfAR's director of research, says she hopes the grants will catalyze renewed interest in a scientific pursuit that has languished beneath a cloud of embarrassing memories. 'People became very reticent to use the word cure,' she says, recalling the mid 1990s, when scientists made what proved to be faulty claims that triple combination therapy might fully eradicate HIV. 'It's the four-letter word of AIDS research.' During the press conference where the Gates Foundation's efforts were announced, Melinda Gates said a vaccine might take an additional 15 to 25 years to develop, but in the meantime, microbicide research could yield an 'interim hope.' (A foundation spokesperson, however, declined to comment on whether this remark indicated plans for ramped-up microbicide spending.) 'We have all been frustrated by the slow pace of progress in HIV vaccine development,' says Jose Esparza, senior adviser on HIV vaccines for the Gates Foundation, 'yet breakthroughs are achievable if we aggressively pursue scientific leads and work together in new ways.' But according to Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition, although the grants will raise the current global spending on vaccine development from $750 million to $800 million per year, that number is still short of the estimated $1 billion to $1.2 billion needed. And amfAR's goals seem no less lofty, considering the track record of treatments. Efforts to eradicate HIV through antiretroviral therapy have been frustrated by the virus's ability to hide from the medications. HIV not only harbors itself in lymph nodes and other 'reservoirs' but cannot be destroyed by antiretrovirals when it is inside a CD4 cell during the latent phase of the immune cell's life cycle. Consequently, much of the amfAR research focuses on these particulars of the virus. 'I think the time is right for this research,' says Steven Deeks, an associate professor of medicine at the University of California, San Francisco, and an amfAR grant recipient. 'People are once again talking about eradication.'' The Gates Foundation intends to use its largesse to not just create but better coordinate the search for the elusive vaccine. To date, most research has been conducted by independent groups that usually are using different yardsticks for evaluating their data. The 165 researchers receiving Gates funding have agreed to share their research results with one another. Five of the grants, totaling $92 million, will go toward establishing central facilities at Duke University and the National Institutes of Health, among other institutions, that will assist the members of the research consortium in pooling their findings according to standardized protocol. The remaining 11 research grants are split between two scientific approaches: eliciting neutralizing antibodies against HIV, and creating cellular immunity to the virus. Sandhya Vasan, a member of David Ho's team at the Aaron Diamond AIDS Research Center, which is researching vaccines that target the immune system's dendritic cells, says the Gates Foundation is taking an active role in controlling the content of the grants in order to ensure that research covers as many bases as possible and is not redundant or ineffective. 'They're different from the NIH, which will just evaluate your idea, and if they say it's good, they'll give you the money and you'll run with it,' Vasan says. 'The Gates Foundation is very much taking a venture capital model where they're going to be very involved.' And amfAR grant recipient Deeks, who will study 'elite controllers''sometimes called 'nonprogressors,' the rare HIVers who are able to control their virus without medications'says the searches for a vaccine and for a cure are actually complementary enterprises. 'Vaccine efforts to completely prevent infection may not be feasible,' he says, 'so efforts at making a vaccine in which complete control occurs subsequent to infection now seems more exciting and feasible.' Vasan adds that such a vaccine could be less than a decade away and could greatly reduce infections, since vaccinated HIVers would have lower viral loads. But even if contributions to vaccine development are the ultimate result of amfAR's research, Johnston doesn't want the world to forget about the 40 million people who are currently infected with HIV. 'My concern is that if and when we have a vaccine one day,' she says, 'people are going to wipe their hands and walk away and figure that their work is now done. But what are we going to do for people who are positive? We can't abandon those people.'