Imagine 90 percent of all people living with H.I.V. diagnosed and treated with drugs. Would it be enough to end the AIDS epidemic?
Researchers attempted to answer the question I  n three enormous studies published on Wednesday in the New England Journal of Medicine. Instead of simply calling on people to get testing and treatment of HIV, health workers in five African countries went to the door, or set up mobile websites, offering tests for HIV, tuberculosis and other diseases to all in some communities .
The one who tested positive for the infection was set up at the clinical time to receive antiretroviral drugs. Subsequently, the investigators assessed whether these efforts made any difference in the number of new H.I.V. infections in these communities.
"Some of us were hoping for a higher decrease in incidence," says Dr. Carlos del Rio, Head of Scientific Advisory Committee at CEO's Emergency Plan for AIDS Relief, or Pepfar, who helped finance the studies. "But at the same time, it is not trivial. A 30 percent decrease in incidence is quite dramatic." in 2018. Epidemic continues to devastate Africa: About 26 million people on the continent have H.I.V, of which only 16.5 million receive drug therapy.
One of the new studies, called Ya Tee (a reference to teamwork in the Setswana language), focused on 15 pairs of villages in Botswana, while one second, called Search , examined 32 rural communities in Kenya and Uganda. The largest of the three studies, PopART, looked at 21 communities in Zambia and South Africa.
In total, the studies cost more than $ 200 million and included nearly 1.5 million people.
"The scale and extent of these studies are remarkable," says Dr. Wafaa El-Sadr, and H.I.V. expert at Columbia University in New York and leader of a group that helped finance PopART . "This is public health research at its best."
To lower the epidemic, the United Nations set  "90-90-90" targets for 2020: diagnosing 90% of people infected with HIV; treat 90 percent of those diagnosed with antiretroviral treatment, regardless of the stage of the disease, and keep the virus suppressed in 90 percent of those treated.
If this strategy was successfully implemented, it would leave nearly three quarters of infected individuals with such low levels of H.I.V. in their blood they would not be able to infect anyone else. The new studies were the first to attempt the so-called universal test and treatment method, and all outperformed the goals 90-90-90.
Each study was designed differently, but basically, the law was randomized throughout communities to receive either the standard of care for that country or a combination of treatments, including testing for HIV, TB and sexually transmitted infections. advice; condoms; prenatal care; and voluntary medical circumcision.
Each study came to approximately the same 30 percent figure for the case of the incidence. However, given the size and complexity of the studies, the details are not simple.
A key assessment from all three studies was the importance of a "warm handoff": Community health workers ensured that everyone who tested positive for H.I.V. Appeared at a clinic for treatment. They called or texted people to remind them of their meetings and escorted them to clinics when needed.
"Some people of so many reasons do not show up," said Dr. Shahin Lockman of Harvard University, who led Ya Tee's. "They're scared, they're not ready, they're worried, they're busy. "
A lack of follow-up may explain why another trial, called TasP, did not find any effect on H.I.V. frequency. The study, funded by the French government and published last year in The Lancet, was conducted in KwaZulu Natal in South Africa and did not meet the treatment goals.
"Link to care was the critical weakness of TasP," said Doctor Gilles Van Cutsem, an advisor to the medical charity Doctors Without Borders, who was not involved in the recent studies. "It's the hardest part to achieve."
Given the scope of the three new studies, the researchers expected their analyzes to be complex. But the law also encountered unexpected snags.
In 2013, the trial standard in these countries was only to offer antiretroviral drugs to HIV-infected individuals with a CD4 speech – a measure of certain immune cells in blood – of 350 or less. (The range for a healthy person is 500 to 1500.)
However, in 2016, the countries began offering universal treatment – that is, antiretroviral drugs to anyone who is H.I.V. positive, regardless of CD4 speech – even if it is not universal test.
The change was good for the patients, but it made it difficult, and perhaps even unnecessary, to assess the benefits of universal treatment.
The switch had the greatest impact on PopART, which divided its 21 communities into three groups: one received universal testing and treatment, while the other received universal testing but treatment according to local guidelines. The third group held local guidelines for both testing and treatment.
When countries switched to universal treatment, the first two groups were "essentially identical," Dr. Richard Hayes, an epidemiologist at the London School of Hygiene & Tropical Medicine, co-author of popART. "When we originally designed this study, we never expected such a rapid change."
Although both groups were identical, only the other showed a 30% decrease in H.I.V. incidence – a result that hitherto stumps the researchers. (The first group showed a decrease of 7 percent, but it was not a statistically significant result.) "19 Oh, my God, tell a weird find," Dr. Del Rio said. "I don't know. I don't know what to do about it."
While trying to solve the mystery, Dr. Hayes and his colleagues have chosen to combine the results of both first and second groups and reported a cumulative reduction in the incidence of 20 percent.
The search study also had its share of problems. The fact that the team's approach included tests for chronic diseases such as diabetes and hypertension, and investigators saw a 32 percent decrease in H.I.V. infections.
But the comparison group also showed a similar drop – perhaps because the researchers also offered the complete test package even to people in that group, says Doctor Diane Havlir of the University of California, San Francisco, who led the study.
However, the team saw a 23 percent decrease in HIV death and 59 percent reduction in TB infections among people with HIV Testing of a number of diseases is useful and realistic, Dr. Havlir, as it reduces stigma and makes it easy to register patients in care about many conditions.
"If you're not just doing it for H.I.V. and you're determined to build the care for these other diseases, it's a common cost," she said.
In all the new studies, the health workers had the greatest problem reaching men and young people for H.I.V. testing. Some of the teams tried to set up tents and camps near farms, taxi stations, schools and sporting events, and even drove them on weekends and evenings.
"Men go from having a pediatrician to a geriatrician, it has been a consistent result in global health," says Dr. Del Rio. "It also shows where we need to make a lot of our efforts."
But these efforts are unlikely to be performed on anywhere near the scope of these new studies, partly because of expense, and because universal treatment has already become standard.
"These are all really important studies, but never again will they be performed," says Dr. Del Rio. "Because the world has changed, we will not see this again."