Another possible HIV cure case after stem cell transplantation for cancer; example of extended post-treatment control in Spain

The 24th International AIDS Conference (AIDS 2022) officially opened on Friday in Montreal, but a Zoom press conference two days earlier shared news of results from several studies, including two case reports relevant to HIV cure research. [1]

Jana Dickter from the City of Hope hospital in Los Angeles described another instance of “prolonged HIV-1 remission” after receipt of a stem cell transplant required to treat a life-threatening cancer, this time in a 66-year-old man. The stem cell donor was homozygous for the CCR5 delta-32 mutation, which causes immune cells to be resistant to most HIV variants. Dickter emphasised the unique aspects compared to previously reported cases:

• The person was older (63 at the time of the transplant procedure, 66 now).
• Has been living with HIV longer (over 31 years).
• Received a less immunosuppressive regimen during transplantation and a chemotherapy regimen that is better tolerated by older people.

As explained in a press release from the City of Hope, the stem cell transplant was administered in early 2019 after a diagnosis of acute myelogenous leukemia (AML). [2]

Antiretroviral therapy (ART) was stopped in March 2021 and the man has now been followed for over 17 months with no HIV viral load rebound or HIV DNA detected. Antibody responses against HIV have waned and virus-specific T-cell responses are no longer detectable. The AML is in remission.

Dickter noted that the particular protocol employed at City of Hope is likely better suited to older people with HIV who require stem cell transplants to treat cancers, and may offer additional opportunities to attempt cures if appropriate CCR5Δ32 homozygote donors can be identified.

As with the New York City woman reported at CROI earlier this year, the researchers are being cautious and using the term remission to describe the case rather than cure, due to limited follow-up. [4]

It would be helpful for the HIV cure research field to come to consensus on how best to define cure in such cases, because news coverage tends not to adhere to these distinctions in terminology.

There’s also an urgent need for consensus on how many cases of HIV cure/remission have been achieved by stem cell transplants from CCR5 delta-32 homozygote donors: both the International AIDS Society and City of Hope press releases erroneously state that this represents the “fourth” such case but in fact, as reported for NBC News by Benjamin Ryan, there are five in total: [5]

• Timothy Ray Brown (aka the Berlin patient).
• Adam Castillejo (aka the London patient).
• The Düsseldorf patient.
• The New York patient.
• The City of Hope patient.

Details on each of the prior cases is included in TAG’s latest Research Toward a Cure and Immune-Based Therapies Pipeline Report. [6]

Dr. Núria Climent delivered the second report, about a case of “exceptional post-treatment control” in a woman with HIV who’d participated in a clinical trial in Barcelona. The Hospital Clínic-IDIBAPS have issued a press release about the findings. If I’m understanding correctly, it also involves an older individual: the woman was 59 at the time of study enrollment and so is in her 70s now. [7]

The study was complicated, beginning by randomising people with recent HIV infection to receive either ART or ART plus the immunosuppressant drug cyclosporine. There was a total of 20 participants: 19 cisgender men and the one cisgender woman (who was assigned to receive ART plus cyclosporine). Results from this initial part of the study were published in 2016. [8]

The woman was then rolled over into another protocol that involved an analytical treatment interruption (ATI). [9]

A short course of GM-CSF and pegylated alpha interferon was given during the ATI, followed by another period of ART plus subcutaneous low-dose IL-2 before treatment was interrupted completely.

The crux of today’s report is that the participant has now maintained an undetectable HIV viral load for more than 15 years off ART and has displayed a progressive decline in measures of the HIV reservoir during that time. HIV that’s capable of replicating can still be detected at low levels, however, suggesting that control is being actively maintained by the immune system.

In laboratory tests, the researchers identified “memory-like” natural killer cells and gamma-delta CD8 T cells as contributors to suppressing HIV replication (these represent relatively small subsets of immune system cells whose potential role in suppressing HIV hasn’t received much attention historically).

The woman does not have any genetic factors that have been associated with immunological control of HIV, and Climent explained that she experienced quite severe symptoms during primary infection (which was diagnosed at Feibig stage 5).

In response to questions, Climent noted that the woman was the only study participant who experienced post-treatment control, so the role (if any) of the immune-based interventions that were given is unclear. The researchers have also not tested for the presence of antiretrovirals in blood samples, which is necessary to confirm that the viral load control has occurred post-treatment. The formal presentation at the conference will occur on Sunday July 31. [10]

There’s been at least one other report of extended post-treatment control in a person who received ART plus cyclosporine during early HIV infection. That case, described by researcher Guiseppe Pantaleo in 2009 as “the Lausanne Patient”, was a man who had been off ART for over eight years at the time of the report. [11]

HIV cure research might potentially benefit from compiling all the historical reports of post-treatment control and assessing their current status (if the information is available). So far, the phenomenon appears rare, but it has the potential to offer clues to help develop curative interventions.