With HIV Prevention Possibilities on the Rise, an African Cohort Closes in on a Last Checkup

In 2006, a group of 613 people recently infected with HIV from Uganda, Rwanda, Zambia, Kenya, and South Africa volunteered for a scientific study group led by the International AIDS Vaccine Initiative (IAVI). This extensive study became known as Protocol C and is the largest acute infection cohort in Africa.

While only about a third of the volunteers are still in the cohort, studies of these individuals are still providing insights. This cohort was the source of a series of broadly neutralizing antibodies that are unusually good at neutralizing HIV and are now serving as a tool to design vaccine candidates capable of preventing HIV infection.

The possibility of amassing and studying cohorts of acutely HIV-infected individuals, such as those in Protocol C, may be diminishing. The recent success of new methods to prevent HIV from taking hold in the first place—including pre-exposure prophylaxis (PrEP) which is already an approved HIV prevention strategy in the US—may affect, in as-yet-uncertain ways, the ability to do this type of long-term study and what will be found by researchers working with these individuals. Yesterday, away from the conference, it was reported that the placebo arm of a European trial studying the antiretroviral Truvada used as PrEP will be stopped early and volunteers will be offered the antiretroviral because of its observed effectiveness at preventing HIV infection. What’s unique about this study, known as IPERGAY, is that the drug was only administered intermittently, around sex, rather than on a daily basis. That this strategy appears to work so decisively is a clear demonstration of the versatility of antiretroviral-based prevention, and could be a big boost for the acceptability of PrEP.

“Timelines are going to change,” says Imperial College immunologist Robin Shattock, a co-chair of the HIVR4P congress currently winding down in Cape Town, South Africa. “The environment is going to change.” Shattock himself is currently undertaking research into the potential effects of combining a microbicide and an experimental vaccine candidate.

While most quarters see advances in PrEP as progress, this strategy is getting some push-back from sex workers worried about losing leverage in demanding condom use from clients. And researchers understand use of PrEP and other HIV prevention strategies may limit their ability to study the natural evolution of antibody responses in HIV-infected individuals. Researchers such as Elise Landais, a research associate with Pascal Poignard’s group at The Scripps Research Institute’s IAVI Neutralizing Antibody Center, are making the most of IAVI Protocol C while it lasts. “It is probably our last chance to look at natural broadly neutralizing monoclonal antibody responses in a natural infection setting,” she says.

Landais, who’s been working with the Protocol C group for some time now (see ‘Out of Africa,’ near end ofTapping the Sanguine Humor), presented her latest findings in Cape Town earlier this week at HIV R4P. In the search for neutralizing antibodies, Landais says the rare volunteers in the group who develop them start doing so after two years of infection, with increasing levels of antibodies until 48 months after infection, until they reach a plateau. “Overall we identified seven individuals,” Landais says of the original protocol group, “with a transition score higher than two.” That means their antibodies are effective in neutralizing 80% of viruses in a panel of several strains of HIV.

One other potentially interesting finding from the Protocol C cohort is the identification of higher levels of memory T follicular helper (Tfh) cells in the blood, cells that have both transcriptional and functional properties. “Even at an early and late point,” Landais says, referring to the amount of time a volunteer’s been diagnosed with HIV infection, “we found more of these cells in the blood of the top neutralizers.” Researchers think understanding the biology of memory Tfh cells will also boost understanding of autoimmune diseases and of how vaccines work.

The ongoing Cape Town congress is itself a sign of change, aimed at bringing together researchers pursuing their different aims in vaccines, pre-exposure prophylaxis, and microbicides along with community members, policymakers, and advocates.

Rare and mighty as their contributions are, the window may be closing on volunteer groups like Protocol C. But for the next generation, the horizons are expanding. – Michael Dumiak