Prolonged Remission in Patient With HIV May Open New Avenues to Functional Cure

Kate Johnson

July 29, 2022

The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers of the International AIDS Conference (AIDS 2022).

Although the 59-year-old woman is one of many who are known as post-treatment controllers (PTCs) — having been in remission for more than 15 years after stopping antiretroviral therapy (ART) — it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

"This case opens new avenues in the HIV functional-cure field," lead investigator Núria Climent, PhD, of Hospital Clinic-IDIBAPS/University of Barcelona, HIV Unit, Barcelona, Spain, told Medscape Medical News in an interview.

"As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses," she said, explaining that these cells "have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors…but also mediated by early ART treatment and might be by the immuno-mediated treatment."

The findings suggest the potential for "increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure," she said, adding, "As far as we know, aiming to increase these specific cells has never been done before in people living with HIV."

In a press conference during the meeting, Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy (J Antimicrob Chemother. 2017;72:829-836). This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

"None of the other 19 patients included in the trial controlled viral replication," senior investigator Jose Miro, MD, PhD, also from Hospital Clinic-IDIBAPS/University of Barcelona, HIV Unit, Barcelona, Spain, told Medscape.

Sharon Lewin, MD, president-elect of the International AIDS Society (IAS), which runs the conference, told Medscape that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting.

"It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it's important [that] they can explain it to them."

Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, added that it is impossible to determine the mechanism of action from a single case report. "We don't know if the intervention played a role or if this person is a 'post-treatment controller,' which has been previously described many times," she told Medscape. "In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it's still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don't think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission."

Climent has disclosed no relevant financial conflicts of interest. Lewin has disclosed i nvestigator-initiated industry-funded research (Gilead, ViiV, Merck ), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, BMS).

24th International AIDS Conference (AIDS 2022); July 29-August 2, 2022; Montreal, Quebec, Canada. Abstract 5149. Presented to the press July 27, 2022.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.

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