Treatment as Prevention

In advance of today’s World AIDS Vaccine Day, a May 16 symposium sponsored by the New York Academy of Sciences (NYAS) provided an array of talks that largely focused on the progress and challenges in developing an AIDS vaccine. Michael Watson, who leads the global immunization policy group at Sanofi-Pasteur, noted during his opening that HIV scientists have made great strides in recent years, but that we “still don’t fully understand the enemy and how our bodies react to that enemy.”

But there were more than vaccines on the menu.  The opening keynote at the NYAS session, “Cracking the Safe: Advances in HIV/AIDS Prevention and Treatment,” presented by Myron Cohen of the University of North Carolina, showcased recent results from a widely publicized study that found early treatment of HIV dramatically lowers the risk of transmission to uninfected partners. Cohen was principal investigator of this Phase III randomized study, known as HPTN 052, which enrolled 1,763 serodiscordant, mostly heterosexual couples, at 13 sites in Africa, Asia, and North and South America, and cost US$73 million. 
The study enrolled couples whose HIV-infected partners had CD4+ T-cell counts ranging from 350-550 cells per milliliter of blood. Half of the infected partners started antiretroviral (ARV) therapy immediately, the other half delayed treatment until their CD4+ T-cell counts dropped to within 200-250, or they had developed an AIDS-defining illness. Four years before the study was due to finish, an independent Data Safety Monitoring Board (DSMB) concluded that early initiation of ARVs led to a 96% reduction in HIV transmission among uninfected partners of study participants who began ARV treatment earlier. The DSMB informed the study’s funder, the US National Institute of Allergy and Infectious Diseases (NIAID), to release the results as soon as possible and to share the findings with participants and investigators. 
In its review, the DSMB found a total of 39 new HIV infections among uninfected partners. Of those, genetic analysis showed 28 were linked to the infected partners, seven were not linked to the HIV-infected partner, and four were still being analyzed. Of the 28 cases linked to the HIV-infected partner, 27 occurred among those whose partners were randomized to the delayed-treatment arm of the study. 
“That was a powerful prevention message,” said Cohen, adding that he was shocked when NIAID informed him of the findings. “When we were called to Washington, I thought it meant that the study had gone badly.”
Cohen said study participants also demonstrated “remarkable adherence” to their daily ARV regimens as measured by monthly drug-detection tests, suggesting that altruism is a powerful force for compliance. Cohen said couples may have taken pills faithfully every day because they were contributing to the health of their spouse as well as themselves.
There were also only 40 clinical events in the early treatment arm compared to 65 in the delayed treatment arm. Most notable, perhaps, was the number of cases of pulmonary tuberculosis—a leading opportunistic infection among HIV-infected adults in the developing world. There were just three cases of tuberculosis in the early treatment arm compared to 17 in the delayed treatment arm. 
Cohen said the results of HPTN 052 do not mean we can “treat our way out of the epidemic,” adding that early testing and immediate treatment won’t capture the majority of acute infections, where the levels of HIV in semen and blood are higher and therefore more likely to lead to HIV transmission. “The HPTN 052 study definitely showed that ART reduces transmission of HIV, but the public health use of this [test and treat] strategy has some real public health challenges,” said Cohen. “Nonetheless, the horse is out of the barn, so to speak.” 
The NYAS conference, held the week of World AIDS Vaccine Day, which is commemorated today, also included updates on the post-RV144 trial analysis. Jerome Kim, deputy director of science at the US Military HIV Research Program, a key collaborator in the 16,000-person trial, said the long-awaited case-control study to try to determine immune correlates of protection is finally underway. After lengthy discussion, researchers settled on six primary assays, five to measure antibody responses and one to measure cellular responses. 
The day-long NYAS symposium also highlighted research on combination-prevention approaches. Cecilia Cheng-Mayer, a professor and staff investigator at Aaron Diamond AIDS Research Center in New York, presented results of a non-human primate study looking at whether a prime-boost vaccine candidate and a microbicide achieved higher efficacy than when the interventions were used independently. The study found the combination strategy led to fewer HIV transmissions and a slower rate of disease among the Asian rhesus macaques that became infected following vaginal challenge.