In the spirit of this exciting era of combination HIV prevention, this update contains breaking news on two different strategies—vaccines and ARV-based prevention—which we hope will someday be part of potent combination HIV-prevention packages, along with many other evidence-informed strategies.
For now, the developments on ARV-based prevention are of immediate relevance to advocates worldwide tracking PEPFAR-country planning processes (due to finish in October 2011) and Global Fund Round 11 applications (due December 2011). As described below, the PEPFAR Scientific Advisory Board met this week and reviewed draft recommendations that would chart a course for the US bilateral AIDS program to use treatment in HIV-positive people as a key prevention strategy. The vaccine update is equally exciting, though with a longer-term horizon.
New signals in AIDS vaccine research
“Now we have informed hypotheses. We have directions. We have signals.” That’s how Bart Haynes of Duke University explained the significance of new information on why exactly the vaccine strategy evaluated in the RV144 Thai Prime-Boost vaccine trial provided modest protection. These major findings were described during Tuesday’s plenary at the AIDS Vaccine Conference in Bangkok.
Audio and video of the scientific presentation can be downloaded here, and a highly informative, layperson-oriented press conference is also available online.
Over the past two years, in the search for clues about why the RV144 vaccine regimen had modest effect, an international team of scientists looked at blood samples from volunteers who had received the vaccine and became infected, those who had received the vaccine and remained HIV-negative, and placebo recipients. They searched for various immune responses in these samples and compared their presence or absence across the various groups.
What they found was that vaccine recipients who remained uninfected had antibodies specific to the V1/V2 region, or loop, on the protein found on the outer coat of HIV. Dr. Haynes said that these antibodies correlated with the lowest risk of infection among vaccinated individuals. The analysis also found that there was greater risk of HIV infection among those vaccine recipients with higher levels of the IgA antibody against HIV outer coat proteins. This finding doesn’t mean that the vaccine put people at risk—but that having higher levels of IgA made vaccine recipients’ risk comparable to people who hadn’t received the vaccine at all.
There were only three milliliters of blood per RV144 participant available for these analyses. This limited the number of tests that could be performed on the samples, and made the chances of getting a clear answer quite small, especially since no one knew exactly what to look for.
Under these circumstances, the fact that the correlates analysis did generate some clear hypotheses is in many ways remarkable. It underscores the importance of international and inter-institutional collaborations. The success of the effort also speaks to the integrity of the process by which the assays (tests) used to hunt for the correlates were validated and selected, and to the valuable contributions of “big science” style consortia that bridge many institutions to the search for a vaccine. The process of selecting and validating assays, and of building the collaborative process, was described in the press conference and in RV144 trial co-principal investigator from the US Military HIV Research Program Jerome Kim’s plenary presentation.
In brief, these findings are significant both for their validation of the process by which they were gleaned—a well-resourced, transparent, collaborative effort—and for the clues they provide for future vaccine design. “We now have clues. This is something we haven’t had over past 30 years. That’s very important for the field,” said Dr. Haynes. He was then asked whether, given the small number of samples, he was surprised that a correlate was identified. The answer: “Yes.”
In the coming months, particularly in the next issue of Px Wire (coming in early October) and in AVAC Report 2011 (coming in time for World AIDS Day 2011), we’ll delve into the findings and what they tell us—and what they leave unanswered.
Integrating recent treatment as prevention results into PEPFAR programming
On Wednesday, September 14, thousands of miles away from Bangkok in Washington, DC, the Scientific Advisory Board for PEPFAR met in a meeting to discuss how to integrate the findings from HPTN 052 into PEPFAR operations.
At the meeting, Mike Cohen of the University of North Carolina and principal investigator of HPTN 052, gave a brief summary of the trial findings. He emphasized the importance of continuing the trial until its scheduled completion (an additional three years—five years in total) in order to measure the durability of prevention benefit observed after a little more than a year of the trial had passed. The initial finding, which prompted the trial to end randomization early, was that HIV transmission risk was reduced by 96 percent in couples where the HIV-positive partner started treatment at CD4 cells between 350 and 550, compared to couples where the HIV-positive partner initiated treatment in accordance with prevailing guidelines (usually around 250 CD4 cells). He also explained that more data are needed to learn more about opportunistic infection complications and rates of CD4 decline in HIV positive participants in the 052 study who started treatment according to national guidelines.
Wafaa el Sadr of Columbia University and the International Center for AIDS Care and Treatment Programs presented draft recommendations for operational guidance, on behalf of the Scientific Advisory Board’s 052/Treatment as Prevention Working Group. A lengthy discussion ensued with some of the best minds in the field. The following are some of the key points that emerged.
Draft recommendations from the Working Group (listed in order of priority):
- Accelerate scale-up of treatment for all with a CD4 cell count <350.
- Offer treatment to all pregnant women for life—regardless of CD4 cell count.
- Offer treatment to all in “recognized” serodiscordant couples—regardless of CD4 cell count. (“Recognized” is defined here as a couple in which there have been one or more episodes of sex per month in the past three months or more.)
- Offer expanded voluntary counseling and testing, and treatment and care to those with changing partners—but not above CD4 cell count 350.
Members of the Scientific Advisory Board agreed on the recommendation to scale up treatment for all people with HIV with CD4 cell counts of 350 or below. This is in line with the current World Health Organization treatment guidelines. In the discussion, participants grappled with the other recommendations, raising issues of cost, feasibility, health benefits for the HIV-positive individual, and the thorny issues of how to prioritize when treatment at CD4 <550 cannot be offered to all. The immediate prevention benefit for pregnant and breastfeeding women and discordant couples was emphasized.
As a next step, the PEPFAR Scientific Advisory Board will edit the draft recommendations to reflect the meeting discussion. These will then be submitted to the Office of the US Global AIDS Coordinator for consideration. They are not necessarily binding recommendations and will not immediately translate into policy and therefore need strong community support. Many advocacy groups, including AVAC, are working in coalition to urge President Obama to use PEPFAR programs as part of a bold strategy to end the AIDS epidemic in our lifetimes—a long-term task that is within reach due to findings like HPTN 052. In the coming weeks, we will be following PEPFAR guidance on HPTN 052 closely and looking to clear leadership from the White House in the work to end AIDS.
Also of key interest to advocates: at the same Scientific Advisory Board meeting, John Blandford of the US Centers for Disease Control and Prevention presented initial modeling data suggesting that expanding ARV treatment to HIV-positive people at CD4 cell counts above 350 would not only have a significant impact on incidence, it would also be cost-effective in terms of the dollars spent per life-year saved when the full benefits of treatment to society are considered.
Want to know more about how such models work? In the coming months, AVAC will be working with our partners to build “modeling literacy” through webinars and downloadable materials. Interested in strengthening your role in a powerful coalition to demand leadership in ending AIDS from governments worldwide? Visit avac.org and watch this space for updates on key developments on policy, implementation and research fronts.