Interesting but Unproven HIV Treatment for “Sao Paulo Patients” | Science

A 36-year-old man in Brazil seems to have cleared the HIV infection. This proved to humans the principle of a new drug strategy designed to flush AIDS virus from all reservoirs in the human body. After receiving a particularly aggressive combination of antiretroviral drugs (ARV) and nicotinamide (vitamin B3), a man who demanded to be called a patient in São Paulo to protect his privacy received all HIV in March 2019. The treatment is stopped and the virus returns to his blood.

The story of the patient is "notable," says Steven Deeks, an HIV/AIDS clinician at the University of California, San Francisco, who was not involved in the study. But others, including him and research leaders, warn that success is not long enough and definitive to label it as a cure. "Interesting anecdotes have long driven the field of HIV treatment. They should be viewed primarily as observations that generate hypotheses that can simulate new areas of research," he said. Says Deeks.

Most people who suppress HIV with ARV and then discontinue treatment see the HIV return to high levels within a few weeks. Not only did the São Paulo patient experience no rebound, his HIV antibody also fell to very low levels, suggesting that he might have cleared infected cells in the lymph nodes and intestines.

Ricardo Diaz of the University of São Paulo, a clinical researcher conducting the trial, says he does not know if the patient has healed. "He has very few antigens," Diaz said, referring to HIV proteins that provoke antibody production and other immune responses. However, he points out that his team has not sampled the lymph nodes and intestines of men with the virus since he discontinued treatment. Diaz talked about the patient at today's press conference AIDS 2020Virtually this week's 23rd International AIDS Conference, he will announce the study tomorrow.

Only two have been found to cure HIV infection: a man who asked to be called Timothy Ray Brown. Patient in londonBoth received a bone marrow transplant as part of their cancer treatment. The transplant cleared the infection and created a new immune system that resisted the virus. However, bone marrow transplantation is an expensive and complex intervention that can have serious side effects, making it an impractical treatment for 38 million people currently infected with the AIDS virus.

Other potential HIV treatment cases have received media attention only to confirm that the virus returns after a long absence. Most calmly, a baby in Mississippi who started ARV shortly after birth was thought to have stopped treatment at 18 months and healed the virus. Suddenly surfaced after more than 2 years.. With a few adults who received a bone marrow transplant Looks like healed It wasn't.

HIV has been found to be particularly difficult to eliminate because it interweaves genetic material into human chromosomes, puts them into a dormant state, and escapes immune surveillance, which usually eliminates foreign invaders. These quietly infected cells are likely to survive indefinitely. It has stem cell-like properties and can clone itself. The researchers came up with Several strategies for flushing cell reservoirs This hides a potential HIV infection, but none is effective.

To compare different reservoir cleanup strategies, in 2015 Diaz and colleagues recruited patients in São Paulo and other individuals who were controlling HIV transmission from ARV. The most aggressive approach used by this man and four others added two ARVs to the three already taking in hopes of eliminating HIV, which may have overturned standard of care. Did. In addition to this "enhancement", the research group received nicotinamide. Nicotinamide, in theory, can "wake up" latent viruses in infected cells. When their cells make new HIV, they either self-destruct or are vulnerable to immune attack.

After 48 weeks on this enhanced schedule, five study participants returned to their usual three-drug regimen for three years and then discontinued all treatment. Four saw the virus returning soon, but a patient in São Paulo 66 weeks have passed No signs of infection. A sensitive test to detect the genetic material of the virus did not detect HIV in the blood. A more sensitive test that mixed his blood with cells susceptible to HIV infection did not produce newly infected cells.

Interestingly, during the nicotinamide fortification period, this man was the only one in five who had the virus detected twice in a standard blood test. For Diaz, this suggests that potentially infected cells were agitated and were a temporary cause of virus production. “I'm always trying to be a defender of the devil, but in this case I'm optimistic,” Diaz says. "Maybe this isn't good for anyone, as this strategy only worked for one of the five here. But maybe it got rid of the virus. I don't know. I think this is a possibility. ."

Diks said no other than the two who were cured of the bone marrow transplant were aware of any reports of decreased HIV antibody levels after treatment was discontinued. One big, unsolved issue, he says, is whether the man really stopped taking ARV. “I haven't taken HIV medications since March 30, 2019,” says a patient in São Paulo. Diaz will confirm this by examining the blood in men with ARV.

Another question is how fast men develop ARV after they are infected with HIV. Studies have shown that a few people who start ARV treatment shortly after infection are likely to control the virus for long periods of time when the drug is stopped, probably because they did not build large reservoirs of infected cells. I will. Patients in São Paulo began treatment two months after being diagnosed in October 2012. Like most people with HIV, it's unclear when the infection occurred, but I suspect it was June 2012. 2010 is negative.

It is also unknown how nicotinamide evokes silently infected cells. HIV DNA remains latent when it is tightly wrapped around a chromosomal protein called histone. To make a copy of the virus, you need to unspool, and Diaz has shown that nicotinamide can trigger this unspooling in different ways.

HIV therapeutic researcher Sharon Lewin, head of the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, was intrigued by the antibody response. But she emphasizes that it is not a compelling, controlled experiment. “We need to go beyond the case reports of HIV remission,” Lewin says. “I look forward to the long-term remissions of multiple participants in a clinical trial. This is what the field really needs to move forward.”