HPTN 052: Antiretroviral Therapy as HIV Prevention

In the years before HPTN 052, HIV treatment guidelines were largely written from the perspective of the infected individual. The central question was when to start antiretroviral therapy in a person with HIV, and the answer hinged on CD4 count thresholds and the risk of opportunistic infection. That treatment might simultaneously protect an uninfected sexual partner was a compelling hypothesis, but it lacked randomized evidence to move policy.

HPTN 052 was designed to test that hypothesis directly. The trial enrolled 1,763 serodiscordant couples across 13 sites in nine countries, including Malawi, Zimbabwe, India, Brazil, and the United States. The HIV-positive partner, with a CD4 count between 350 and 550 cells per cubic millimeter, was randomly assigned to start antiretroviral therapy immediately or to defer until the CD4 count fell below 250 or HIV-related symptoms developed. Myron Cohen at the University of North Carolina at Chapel Hill led the study, and Marybeth McCauley coordinated its multinational operations.

Over the follow-up period, only one linked HIV transmission occurred in the immediate-treatment group, compared with 27 in the deferred group, a 96% reduction. After reviewing the data in early 2011, the independent data and safety monitoring board recommended releasing the results early, and therapy was then offered to all the HIV-positive partners. The result was named Science magazine's Breakthrough of the Year in 2011.

The implications reached beyond the individual couple. Under treatment as prevention, expanding access to antiretroviral therapy became a population-level prevention strategy as well as a clinical priority. The concept, already theorized in models by Julio Montaner and colleagues, now had direct trial support. Guidelines on when to start treatment now had to weigh the risk to partners as well as the benefit to the patient.

In September 2015 the World Health Organization recommended starting antiretroviral therapy in everyone living with HIV at any CD4 count, a policy known as Treat All that was adopted widely in national guidelines. The final HPTN 052 analysis, published in 2016 after more than five years of follow-up, counted 3 linked infections in the early-therapy group and 43 in the delayed group, a 93% lower risk.