CROI 2019: PopART HIV prevention study brings confirmation but also questions

 Science Speaks is in Seattle this week covering breaking news in HIV research, policies and plans at CROI 2019 March 4-7. Door-to-door HIV counseling and testing, followed by immediate access to treatment led to incidence drops -- but with a caveat . . .

SEATTLE - When the PopART study began in Zambia and  South Africa five years ago, the measures it would test among roughly a million people were so obviously beneficial, that the results it would eventually yield seemed predictable: If HIV counseling and testing as well as links to subsequent care and prevention services were universally available, new infections would drop steeply.

A trial was needed, it seemed, only to justify the ambitious expansion of resources that would be needed if the approach were to go large scale. At the same time, in the aftermath of proof from HPTN 052 that treatment not only prevented illness but transmission, ambitions were beginning to grow anyway, by the time the trial also known as HPTN 071 began.

“People have gone from saying ‘the idea is mad, and should not even be considered,'” Dr. Richard Hayes of the London School of Hygiene and Tropical Medicine, leading the trial said at a 2013 meeting of the National Institutes of Health HIV Prevention Trial Network.“Now more people are saying ‘let’s just do this. Why is a trial needed?’”

As it turned out, this week as Dr. Hayes presented the results of PopArt -- "Population Effects of Antiretroviral Therapy to Reduce HIV transmission," the results revealed much of what was expected, but with a surprise all the same. The trial, sponsored by the National Institute of Allergy and Infectious Diseases, examined outcomes in 21 communities randomly assigned to one of three study groups. In one group of communities trained community health workers went from door to door offering HIV testing and counseling, including links to prevention interventions for those who tested negative. In that group -- study arm A, for those who tested positive for HIV, also were given the opportunity and assistance to begin antiretroviral treatment. The second group -- study arm B -- received the same door to door testing and counseling, as well as links to preventive interventions for those who tested negative. Those who tested positive, however, could begin antiretroviral treatment only if their condition met national guidelines for eligibility -- at the start of the trial an immune system -- or CD4 T-cell count -- diminished by the virus to just 350 cells per microliter of blood. That changed through the course of the study, as the two countries adopted guidelines requiring less advanced illness to start treatment -- first to a count of 500 cells. When both countries adopted guidelines in 2016, to saying everyone diagnosed with HIV should have access to immediate treatment, arms A and B were receiving essentially the same services. The third group  -- arm C -- had access to only the prevailing standards of care in their countries, including local HIV testing services, and access to treatment according to the prevailing country guidelines. It's not surprising that those communities receiving door-to-door interventions saw HIV incidence drop. It is surprising that the significant drop -- of nearly a third -- was in arm B, the group receiving treatment according to national guidelines, rather than arm A, the communities where people diagnosed with HIV had the advantage of immediate access to treatment. Those communities saw HIV incidence drop, but not in statistically significant numbers. Dr. Hayes called the lack of a significant incidence reduction both surprising and inconsistent with other data showing that people on treatment in Arm A achieved high rates of viral suppression -- critical to not transmitting the virus. Researchers are continuing to analyze the data to determine if additional factors contributed to the difference between the two groups receiving interventions. In the meantime, in the years since the PopART trial began, it yielded additional information critical to controlling HIV in the countries, some of which can be reviewed here.