Surprise, skepticism, and hope
The results have prompted surprise, skepticism, and questions from clinicians and researchers.
said Anton Pozniak, MD, from Chelsea and Westminster Hospital in London, who is cochair of AIDS 2020.
“They need a bigger study to see whether or not [the participant] is one of these guys who stopped treatment and might take a year or two, or four, to rebound,” he said. But if other studies replicate the results, the control of HIV in “one in five people would still be huge.”
The rationale behind treatment intensification for HIV remission is that “the three-drug ART regimen was perhaps insufficient to completely block HIV replication” in the reservoirs, even though that replication could be happening below levels detectable with current tests, said Laura Persaud, MD, from the Johns Hopkins University School of Medicine in Baltimore, who is chair of the International Maternal Pediatric Adolescent AIDS Clinical Trial Network (IMPAACT) HIV Cure Committee and was not involved in the study.
“The idea was to see if you could accelerate the decay of the reservoir” if you added medications that targeted different parts of the HIV lifecycle. Symfi, for instance, targets just one step in the viral replication process: the point where HIV RNA reverse transcribes itself into DNA so it can integrate into immune cells. But CCR5 inhibitors block entry of HIV into the cell in the first place, and integrase inhibitors, like raltegravir (Isentress, Merck) and dolutegravir, prevent HIV DNA from integrating into the host chromosome after it has reverse transcribed itself.
Still, recent data suggest that treatment intensification might not be as effective as hypothesized, she said. And the nicotinamide study was in vitro. To what extent this is a direct result of this treatment strategy is unclear.
“It’s hard to believe, in this small study, that this agent [nicotinamide] would have such a striking effect on DNA proviral levels,” she said. “We learn from each of these cases. But this is a single case, with multiple mechanisms that may have contributed to the outcome here. To what extent this is a direct result of this treatment strategy is unclear.”
Only time will tell, and Persaud knows this first hand. Back in 2014, she presented data at another HIV conference on the Mississippi baby who, after 21 months of no treatment, still didn›t have an HIV viral load.
At the time, the baby was hailed as “functionally cured,” but just 6 months later, the virus returned.
Dieffenbach agrees. “There are 10,000 genetic variations that need to be considered, and it all adds up to a unique individual,” he said of the Brazilian patient. “This one is one person, and it’s still early days.”
Counseling patients on niacin supplementation
Some clinicians are already bracing for the flood of people with HIV now wanting to take, or who are already taking, a niacin supplement because of this case, said Laura Waters, MD, from Mortimer Market Centre in London, who is chair of the British HIV Association.
But nicotinamide is different than nicotinic acid, which is what many people mean when they talk about niacin supplementation, according to data from the Office of Dietary Supplements (ODS) at the National Institutes of Health. Nicotinic acid has been used as a supplement for people with high cholesterol for years. Most Americans get more than the recommended daily intake of both types of niacin – 16 mg for adult men and 14 mg for adult women – in their regular diet, according to the 2015/16 National Health and Nutrition Examination Survey.
The Brazilian patient received a total daily dose of nicotinamide of 1000 mg, which is not associated with any adverse effects. Doses above 3000 mg daily can lead to diarrhea and a decrease in platelet count, according to the ODS.
Although Diaz said he doesn’t think people with HIV should run out and start taking a supplement right away, Waters said she sees it as inevitable.
The good news is that if people really are taking nicotinamide – not nicotinic acid – it seems “fairly well tolerated without many side effects,” she said, but added: “I expect shortages of nicotinamide from tomorrow.”
This story first appeared on Medscape.com.