Intensive Anti-H.I.V. Efforts meet with mixed success in Africa

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Imagine that 90 percent of all people with H.I.V. were diagnosed and treated with medication. Would that be enough to end the AIDS epidemic?

Scientists tried to answer the question in three huge studies published on Wednesday in the New England Journal of Medicine. Rather than encouraging people to become H.I.V. To test and treat, health workers in five African countries went door-to-door or set up mobile sites that offer HIV testing, tuberculosis, and other diseases to everyone in certain communities..

Everyone who tested positive for the infection was set up with an appointment at the clinic to receive antiretroviral drugs. The researchers then investigated whether these efforts made any difference in the number of new H.I.V. infections in those communities.

The results of three of the studies suggest that the strategy nowhere leads to the number of new infections with H.I.V. whether incidence is reduced to zero. But all studies showed that the incidence decreased by about 30 percent, and one found a decrease in H.I.V. related deaths.

"Some of us hoped for a higher reduction in incidence," Dr. said. Carlos del Rio, head of the scientific advisory board at the president & # 39; s Emergency plan for AIDS assistance, or Pepfar, that helped fund the studies. "But at the same time, it's not trivial. A 30 percent reduction in incidence is pretty dramatic."

In an effort to delay the epidemic, the United Nations has established "90-90-90" goals for the year 2020: diagnose 90 percent of people infected with H.I.V.; treat 90 percent of those diagnosed with antiretroviral therapy, regardless of the disease stage; and keeps the virus suppressed in 90 percent of those being treated.

If this strategy were successfully implemented, it would be almost three-quarters of those infected with such low levels of H.I.V. in their blood that they could not infect anyone else. The new studies were the first to attempt the so-called universal test-and-treat approach, and they all surpassed the 90-90-90 goals.

Each study was designed differently, but broadly, the teams randomized whole communities to receive the standard of care for that country, or a combination of treatments, including testing for H.I.V., TBC and sexually transmitted infections; accompaniment; condoms; prenatal care; and voluntary medical circumcision.

Each study came to approximately the same 30 percent rate for the reduction in incidence. However, given the size and complexity of the investigations, the details are not clear.

An important finding from all three studies was the importance of a "warm transfer": Community health workers made sure that everyone who tested positive for H.I.V. came to a clinic for treatment. They called or texted people to remind them of their appointments and guided them to clinics if necessary.

"Some people don't show up for so many reasons," said Dr. Shahin Lockman of Harvard University, who led Ya T & S. "They are scared, they are not ready, they are worried, they are busy."

"Linking to care was the critical weakness in TasP," Dr. said. Gilles Van Cutsem, a consultant from the medical charity Doctors Without Borders, who was not involved in the newer studies. "That's the hardest thing to achieve."

Given the scale of the three new studies, the researchers expected their analyzes to be complex. But the teams also had unexpected problems.

In 2013, when the trials began, the standard of care in those countries was to offer antiretroviral drugs only to H.I.V. infected people with a CD4 count – a measure of certain blood cell immune cells – of 350 or less. (The range for a healthy person is 500 to 1,500.)

In 2016, however, the countries all started with universal treatment – that is, antiretroviral drugs for everyone who has H.I.V. positive regardless of CD4 count – although not universally tested.

The change was of course good for the patient, but made it difficult, and perhaps even unnecessary, to assess the benefits of universal treatment.

The switch had the greatest impact on PopART, which split its 21 communities into three groups: one received universal testing and treatment, while the second was universally tested, but treated according to local guidelines. The third group adhered to local guidelines for both testing and treatment.

Once the countries switched to universal treatment, the first two groups were essentially identical & # 39; said Dr. Richard Hayes, an epidemiologist at the London School of Hygiene & Tropical Medicine, who was co-leader of PopART. "When we originally designed this study, we never expected this to be such a quick change."

Although both groups were identical, only the second showed a 30% decrease in H.I.V. raid – a result that so far has stumped the researchers. (The first group showed a 7 percent decrease, but that was not a statistically significant result.)

"Oh my god, talk about a weird finding," said Dr. Del Rio. "I don't know. I don't know what to think about it. & # 39;

While trying to solve the mystery, Dr. Hayes and his colleagues chose to combine the results from both the first and second groups and reported a cumulative 20 percent reduction in incidence.

The Search study also had its share of problems. The team's approach included testing, even for chronic diseases such as diabetes and hypertension, and the researchers saw a 32% decrease in H.I.V. infections.

But the comparison group also showed a similar decline – perhaps because the researchers even offered the full test package to people in that group, Dr. said. Diane Havlir from the University of California, San Francisco, who led the study.

Still, the team saw 23 percent fewer deaths from H.I.V. and 59 percent fewer TB infections in people with H.I.V. Testing for different diseases is useful and realistic, said Dr. Havlir, because it reduces stigma and makes it easy to enroll patients who have many disorders.

"If you don't do it alone for H.I.V. and you're committed to building care for these other diseases, it's shared costs," she said.

In all new studies, health professionals had the greatest difficulty in reaching men and youth for H.I.V. to test. Some teams attempted to set up tents and camps near farms, taxi stands, schools and sporting events and even served them on weekends and evenings.

"Men range from having a pediatrician to having a geriatrician, which is a consistent finding in global health," Dr. said. Del Rio. "It also shows where we have to make a lot of our efforts."

But those efforts are unlikely to be performed on everywhere near the scale of these new studies, partly because of the costs, and because universal treatment has already become the standard.

"These are all really important studies, but they will never be carried out again," Dr. said. Del Rio. "Because the world has changed, we will not see this again."