A 35-year-old Brazilian man who participated in a study that received fortified antiretroviral therapy and vitamin B₃ supplementation for 48 weeks joined a short list of patients undergoing remission HIV If there is no effective treatment.
together Mississippi baby, San Francisco man, 24 year old Thai man, 9 year old South African child, And that London And Berlin In patients, Brazilian men have no detectable viral load and HIV antibody tests are negative for more than a year after treatment is discontinued.
But, like the patients in Berlin and London, I don’t think his remission situation would be broadly applicable to other people with HIV, even if the man remains HIV-free in the future, Said director Karl Diefenbach, National Institute of Allergy and Infectious Diseases, National Institutes of Health AIDS Division.
“I don’t think it can be duplicated,” Dieffenbach said Medscape Medical News.. Researchers should still try to confirm the findings, but perhaps they will “go out and treat another 200 with the same protocol” by studying the unique genetic features and immune system of men. You will learn more.
“Shock and kill strategy”
The man had been treated for HIV since being diagnosed in 2012 and was one in 30 enrolled in a Brazilian study. A multi-intervention study to explore the residual replication of HIV-1: a step towards eradicating HIV and sterilizing treatment — 2016. At that point, his regimen was Efavirenz, Lamivudine, And tenofovir disoproxil fumarate (Symfi, Mylan Pharmaceuticals) and his viral load could not be detected.
He was one in five randomized studies to administer integrase inhibitors. Dolutegravir (Tivicay, ViiV Healthcare), CCR5 receptor inhibitor Maravi rock (Serzentry, ViiV Healthcare), and his regular regimen for 48 weeks, plus nicotinamide 500 mg of one vitamin B3 twice daily.
Nicotinamide is especially useful because of its anti-infective properties. tuberculosis.. In vitro, it also helps reverse HIV latency, said Dr. Ricardo Diaz, a researcher at the Federal University of Sao Paulo who released the data at a press conference at the International AIDS Conference (AIDS) 2020.
“This is a shock and kill strategy,” said Dr. Layla Giron of the Wister Institute in Philadelphia, one of the research investigators. “We performed in vitro studies to ensure that nicotinamide eliminates HIV from cells.”
“The cell machinery has changed a lot,” she said Medscape Medical News.. “And since it’s B vitamins, all five participants had no side effects.”
However, the patient was the only person in the treatment group who experienced a viral load “blip” during treatment. Weeks 16 and 24. Also, low levels of viral DNA were present in peripheral blood spots and rectal tissues at baseline and at week 48. And his HIV antibody dropped from 91.8 RLU at baseline to 58.0 RLU at 48 weeks.
“He showed cell activation, reduced inflammation, and a very deep reduction in antibody titers,” Diaz reported.
After 48 weeks of intensive treatment, the patient returned to a regular regimen for 3 years. He then agreed to attempt to discontinue analytical treatment in March 2019 and discontinue all HIV treatment.
“Interestingly, just before the analysis process was interrupted, the HIV DNA sequence was completely negative,” said Diaz.
Every three weeks for the next 64.7 weeks, his viral load went undetected, and HIV DNA in blood spots went undetected. However, there was one change. In February 2020, male HIV antibody tests were negative.
The team confirmed that he was not yet taking antiretroviral drugs. This may explain the undetectable viral load and was not taking it.
Surprise, skepticism, and hope
The results caused surprises, skepticism, and questions from clinicians and researchers.
AIDS 2020 co-chair Anton Pozniak from Chelsea in London and Westminster Hospital noted this remission because the remission occurred without the invasive stem cell transplant process that patients in both London and Berlin received. Deserves.
“They need more research to see if [the participant] He’s one of these guys who may stop treatment and take 1, 2, or 4 years to recover,” he said. But if other studies replicate the results, “one in five is still huge” HIV control.
The rationale behind enhanced treatment for HIV remission is that the 3-drug ART regimen probably completely blocks HIV replication, even though replication may occur below detectable levels in current tests. Was not enough”. From Johns Hopkins University School of Medicine in Baltimore. He is the chair of the International Maternal and Childhood Adolescent AIDS Clinical Trials Network (IMPAACT) HIV clinical trials committee and is not involved in the study.
When we added drugs for different parts of the HIV life cycle, “we wanted to see if they could accelerate reservoir rot.” For example, Symfi targets only one step in the virus replication process. This is the point where HIV RNA can reverse transcribe itself into DNA and integrate it into immune cells. However, CCR5 inhibitors block HIV entry into cells in the first place, and integrase inhibitors Raltegravir (Isentress, Merck) and dolutegravir prevent HIV DNA from integrating into the host chromosome after it is reverse transcribed.
Still Recent data She said treatment intensification may not be as effective as the hypothesis. And the nicotinamide study was in vitro.
The extent to which this is a direct result of this therapeutic strategy is unknown.
“In this little study, this agent [nicotinamide] “It will have such an amazing effect on DNA provirus levels,” she said. However, this is a single case, and there are multiple mechanisms that may have contributed to the results here. The extent to which this is a direct result of this therapeutic strategy is unknown. “
Only time will tell, and Perseau knows this first move. In 2014, she presented the data at another HIV conference Mississippi baby After 21 months of no treatment, the HIV virus was still unloaded.
At that time, the baby was said to be “functionally healed,” but only six months later, Virus returned..
Diefenbach agrees. “There are 10,000 genetic variants to consider, all of which make them unique individuals,” he said of a Brazilian patient. “This is alone and still in its infancy.”
Counseling patients about niacin supplementation
Some clinicians are preparing for the flood of people who already want to get HIV, or who are already taking it. Niacin To supplement the case, said Laura Waters, MD, Mortimer Market Center, London, chairman of the British HIV Society.
However, nicotinamide is different from nicotinic acid. Nicotinic acid is what many people mean when talking about niacin supplementation, data From the National Institutes of Health’s Department of Dietary Supplements (ODS). Nicotinic acid has been used for many years as a supplement for people with high cholesterol. According to the 2015/16 National Health and Nutrition Examination Survey, most Americans exceed recommended daily intakes of both types of niacin (16 mg in adult men and 14 mg in adult women) in their normal diet. I am.
Brazilian patients have a total daily dose of 1000 mg of nicotinamide and no side effects. Doses above 3000 mg daily diarrhea Decrease in platelet count according to ODS.
Diaz said that people with HIV shouldn’t start taking supplements as soon as they run out, but Waters thinks this is unavoidable.
If you’re actually taking nicotinamide instead of nicotinic acid, it “has a lot of side effects and is quite well tolerated,” she said, but “I expect a deficiency of nicotinamide from tomorrow.” Added.
International AIDS Conference (AIDS) 2020: Summary A1811452, published July 8, 2020.
