Largest HIV prevention study ever delivers thoughtful message | Science

SEATTLE, WASHINGTON-The recipe for ending HIV epidemics seems simple. Introduce generalized tests. Immediately put anti-virus antiretrovirals (ARVs) at undetectable levels so that HIV-positive people do not infect others. The number of new infections will decrease and the epidemic will subside.

But massive and costly studies carried out in recent years have not shown that this strategy can effectively curb the spread of the virus, to the frustration of researchers. The last and largest study ever presented here last week at the Conference on Retroviruses and Opportunistic Infections showed a modest benefit. But, what is confusing, there was virtually no decline in the number of infections in the study group where it was most expected.

Ending the HIV / AIDS epidemic could be more difficult than expected, it seems. "ARVs as such are not the magic bullet," says Collins Iwuji, an epidemiologist at the Faculties of Medicine in Brighton and Sussex, UK, who was involved in one of the previous studies. treatment trial in South Africa.

The new study, entitled Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART), included one million adults in Zambia and South Africa. In its early years of 2013, research had shown that ARVs can not only prevent the disease, but also prevent people from infecting others. But it was not clear whether these benefits would pass from an individual to an entire community.

PopART randomized 21 communities in three arms. One of them was the subject of an annual HIV test at home and immediate treatment for those infected (A); another underwent the same test, but the treatment followed the guidelines in force in the country and was only offered to HIV-infected persons who already had signs of immune damage (B); and the third received no intervention from the study (C).

After three years, an analysis of more than 12,000 people in each of the three branches revealed that group B had 30% fewer new infections than group C. But in branch A, where more people would have been treated, researchers found only 7% fewer infections than in group C, which was not a statistically significant difference. "When we saw the results for the first time, we thought it was the opposite. The results of the A and B arms were reversed, "says Richard Hayes of the London School of Hygiene & Tropical Medicine, who headed PopART. "Four statisticians looked at the data. That's right, I'm scared.

"We have a lot of work to do" to explain the unexpected result, he adds. Among the factors that could have increased the risk of infection in A, there is the migration of infected people, the grouping of sexual networks with highly infectious people or greater sexual risk taking.

François Dabis, director of the French Agency for Research on AIDS and Viral Hepatitis in Paris and principal investigator of the previous study on TasP, is pleased that PopART has at least had an impact on the B arm TasP compared an immediate treatment to a treatment according to South African guidelines; The results, published last year, showed no immediate benefit of immediate treatment for the population, probably because many of those tested positive did not seek the free care available.

SEARCH, a large study conducted in Kenya and Uganda that used health fairs to perform community-level tests, was more successful in treating infected people. But SEARCH investigators reported last summer that they too had arrived empty-handed. In the midst of the trial, both countries adopted the new World Health Organization (WHO) guidelines recommending that all people infected with HIV receive treatment immediately, thus depriving them of HIV. study of his control group. (WHO's recommendations have also complicated the analyzes of PopART and TasP.) A fourth study in Botswana revealed a 30% drop in the number of new cases generated by generalized screening and treatment, but it counted heavily fewer people and did not reach statistical significance.

Diane Havlir of the University of California at San Francisco, one of SEARCH's lead researchers, welcomes the clear message of the studies: widespread screening identifies the majority of infected people as an essential part of the Ending AIDS program ". "We are a little closer and have data for next steps," said Havlir.

Nobody is ready to give up universal treatment either. "We are not going in the wrong direction," says Dabis. "What we're saying is that it's more complex to reduce the incidence than we expected." Like many others, he explains that providing antiretroviral therapy as a pre-exposure prophylaxis to people with a high risk of infection is a key missing element of these studies.

"But we must be humble," says Havlir. The four studies, which together cost more than $ 200 million, have not clarified a central question: what percentage of infected people need to start treatment and completely eliminate HIV for one year? epidemic to degrade? Based on a mathematical model, the Ending AIDS Campaign promoted by the Joint United Nations Program on HIV / AIDS aims to raise the awareness of 90% of people living with HIV, 90% of them in treatment and care. 90% of those infected. those who have undetectable virus levels. PopART A and B arms both achieved this triple target, as did SEARCH and the Botswana study.

But maybe it was not enough. "Ninety-nineteen was an advocacy slogan that translated into programmatic goals," says Kevin DeCock, a Kenya-based epidemiologist and member of the Scientific Advisory Board of PopART, a member of the US Centers for Disease Control. and disease prevention in Atlanta. "It remains to show what is the epidemiological control. We did not get out of the woods. "