HIV Remission: No Transplant Necessary

For over a year, a patient living with HIV has been in HIV remission following structured treatment interruption, and without the aid of a stem cell transplant or myeloablation, a researcher said here.

The man, age 34, was one of five patients to receive a regimen of highly intensified antiretroviral therapy (ART) as part of a 48-week clinical trial. He returned to his regular ART regimen in 2016, and then had a structured treatment interruption in 2019.

His HIV viral load is below the detectable limit and he has undetectable total HIV DNA at 64.7 weeks following treatment interruption, reported Ricardo Diaz, MD, of the University of Sao Paolo in Brazil.

The news caused a considerable stir when it was presented in a pre-briefing for media at the International AIDS Conference virtual meeting, though experts from the conference who were not involved with the study seemed more cautious than optimistic.

"I'm a skeptic, I'm waiting like [with] the London patient until a couple of years have gone by," said International AIDS Society President Anton Pozniak, MD, PhD. However, Pozniak also called the results "exciting."

"Let's see, and follow them out longer, and follow the other four patients in the study," said Monica Gandhi, MD, local co-chair for the conference.

Until now, the highest profile patients achieving HIV remission had undergone bone marrow transplants: both the Berlin patient, Timothy Brown, and the London patient, Adam Castillejo. The latter case was presented at the 2019 Conference on Retroviruses and Opportunistic Infections.

This Brazilian patient was diagnosed in 2012, and was one of five patients in the trial to receive "baseline ART + dolutegravir + maraviroc," as well as 500 mg of nicotinamide, a form of vitamin B3 often used as a dietary supplement.

Dolutegravir is an integrase inhibitor recommended as first-line treatment for people living with HIV by the World Health Organization, while maraviroc is a CCR5 antagonist recommended for patients whose strain of HIV uses the CCR5 receptor, according to the NIH AIDS Info website.

"We knew maraviroc was a latency reversal agent, and it has also been described that nicotinamide has that property ... besides boosting the immune system," Diaz said at a virtual press conference.

He said nicotinamide could be able to reverse HIV latency by two mechanisms. It acts as a histone deacetylase (HDAC) inhibitor to help reverse the latency of cells. It also deacetylates methyltransferase enzyme SUV39, which could also lead to cell latency reversal.

"In animal models, nicotinamide was able to increase CD4 and CD8 activity ... that's our hypothesis ... nicotinamide boosted the immune system of those patients, together with reversing latency," Diaz noted.

Given the effects on this one patient, questions abounded about whether this means all patients with HIV should receive the supplement.

"I don't think it's time to start nicotinamide in every patient ... we do need more data from more individuals than one about how long [this patient] was infected, and we need to watch him longer," Gandhi said.

The initial clinical trial included men, ages 18-65, on first-line ART, with a viral load below the detectable limit for over 2 years, a CD4 nadir of more than 350 cells/mm3, and R5 strains by genotropism.

The man was described as a Brazilian MSM (men who have sex with men), who was HIV negative in 2010. He was diagnosed with HIV and initiated ART in 2012 with AZT/3TC+EFV (zidovudine and lamivudine + efavirenz). He entered the study in September 2015 with a viral load below the detectable limit.

Viral load was monitored every 4 weeks, and he had two viral blips during the study, which ended in September 2016. The authors noted the man had low-level HIV DNA positivity in peripheral blood mononuclear cells (pbmc) and rectal biopsy both at baseline and at week 48.

When the man was invited to proceed with treatment interruption, Diaz said HIV DNA in peripheral blood mononuclear cells (pbmc) was "completely negative."

Diaz said the man provides samples every 4 weeks of pbmcs, blood, urine, and saliva, with the last viral load measurement on June 22. According to public records in Brazil, he has not received ART during this time.

When asked if he has validated these results with an outside lab, Diaz replied, "not yet," but he would "consider making samples available." The authors concluded that, "further assays for viral persistence and longer follow-up [are] needed."

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