A 36-year-old man in Brazil – now called the “São Paulo Patient” – seemingly cleared an HIV infection after receiving an aggressive combination of antiretroviral (ARV) drugs and nicotinamide (vitamin B3). He went off all HIV treatment in March 2019 and has not had the virus return to his blood.
Most people who suppress HIV with ARVs and later stop treatment see their viral load race back to high levels within weeks. What’s interesting in the case of the “São Paulo Patient” is he did not experience a rebound, and – better yet – his HIV antibodies also dropped to “extremely low levels”, which hints at the possibility that he may have cleared infected cells in the lymph nodes and gut (some of the “reservoirs” where HIV may be “hiding” even for people with undetectable viral load).
Now this is important: According to Ricardo Diaz of the Federal University of São Paulo, the clinical investigator running the study, he doesn’t know whether the patient is cured.
Discussing the case at a press conference of the pay-to-access International AIDS Conference (IAC) 2020, which is being held virtually because of the Covid-19 pandemic, Diaz said that the “São Paulo Patient” “has very little antigen” (referring to HIV proteins that trigger the production of antibodies and other immune responses). But they have not yet sampled the man’s lymph nodes or gut for the virus since he stopped treatment.
Only two people are known to have been cured of their HIV infections: Timothy Ray Brown and Adam Castillejo. Both received bone marrow transplants as part of a treatment for cancers, with the transplants clearing their infections and giving them new immune systems that resist infection with the virus.
However, bone marrow transplants are expensive, complicated interventions that can have serious side effects, making them an impractical cure for over 38 million people living with HIV.
HIV is difficult to eliminate because the virus weaves its genetic material into human chromosomes, where it can lie dormant and so escape the immune surveillance that typically eliminates foreign invaders. Researchers have come up with various strategies to “flush” the reservoirs of cells that harbor latent HIV infections, but so far none have proved effective.
Diaz and his team wanted to compare different reservoir-clearing strategies in 2015, leading to the recruitment of the “São Paulo Patient” and other individuals who had controlled their HIV infections with ARVs.
For this study, the most aggressive approach was used in the “São Paulo Patient” and four others, which added two ARVs to the three they were already taking, hoping this would rout out any HIV that might have dodged the standard treatment. The study group also received nicotinamide that can (in theory) prod infected cells to “wake up” the latent virus. So when those cells make new HIV, they either self-destruct or are vulnerable to immune attack.
After 48 weeks on this intensified treatment, the five participants returned to their regular three-drug regimen for three years, and then stopped all treatments.
Four participants saw the virus quickly return, but the “São Paulo Patient” has now gone 66 weeks without signs of being infected, with tests that detect viral genetic material not finding HIV in his blood.
A more sensitive test was done, mixing his blood with cells that are susceptible to HIV infection, and it produced no newly infected cells.
There are also numerous unknowns, e.g.:
- Whether the man indeed stopped taking his ARVs, which has yet to be confirmed with blood examination/s.
- How soon the man started ARVs after becoming infected with HIV.
- How nicotinamide would awaken silent infected cells.
- And if this canoe done/replicated in controlled environment with multiple participants.
“I’m always trying to be a little bit the devil’s advocate, but in this case, I’m optimistic,” Diaz said. “Maybe this strategy is not good for everybody because it only worked in one out of five here. But maybe it did get rid of virus. I don’t know. I think this is a possibility.”