The next Berlin patient: 7th to join pool of HIV patients achieving sustained remission

A new patient achieves sustained HIV remission – the seventh in the world – following stem cell therapy for blood cancer and after stopping antiretroviral therapy (ART), adding to the roster of individuals with HIV who are inching their way towards a potential cure.

“We found treatment-free HIV remission exceeding 5 years without ART in a male individual following allogeneic hematopoietic stem cell transplantation (aHSCT) for acute myeloid leukaemia (AML) with functional CCR5 coreceptors (heterozygous CCR5 wild-type [WT]/Δ32),” said Associate Professor Christian Gaebler from Charité – Universitätsmedizin Berlin in Germany, at AIDS 2024.

Dubbed ‘the next Berlin patient’, this German individual received an HIV diagnosis in 2009. Due to the treatment guidelines at the time, ART was not initiated until April 2015. He was started on a raltegravir-based regimen. Following ART, viral loads dropped below levels of detection.

The patient was diagnosed with AML around the same time he initiated ART. He eventually required aHSCT. Prior to the transplant, total HIV DNA and reservoir sites of 1.78 log copies/10⁶ cells were detected which, according to Gaebler, is neither extremely high nor low when compared against the levels observed in people with HIV.

The clinical team treating the patient was unable to identify a donor carrying the homozygous CCR5 Δ32 mutation, Gaebler shared. Instead, they selected an HLA-identical female donor carrying a heterozygous CCR5 Δ32 mutation. The patient then received reduced-intensity conditioning.

“We observed full-donor chimerism within 28 days, which was maintained throughout … We saw waning HIV-specific antibody and T-cell responses post aHSCT, both in peripheral blood and intestinal biopsies,” said Gaebler. “Of note, looking at the HLA alleles in both donor and recipient, we did not detect any known protective HLA alleles for HIV control.”

In September 2018, ART was stopped. The team was unable to detect any signs of viral activity afterwards, and HIV remained undetectable in plasma for over 5 years after treatment interruption. [AIDS 2024, abstract SS0402LB]

Cure cases rare, but growing

According to Gaebler, a state of HIV cure should enable a person with HIV to safely stop therapy and live a long and healthy life. “This includes strategies for achieving HIV remission through reservoir modulation or immunological control and eradication of the HIV reservoir.”

As per the UNAIDS*, roughly 85 million individuals have been or are living with HIV since the beginning of the epidemic. Despite this staggering number, a scalable cure remains elusive. “I think this highlights how rare HIV cure cases are and what a critical need scalable solutions really are,” Gaebler stressed.

The roster of known successful cases of HIV eradication and cure includes the Berlin, London, Dusseldorf, City of Hope, New York, and Geneva patients.

The first five patients received CCR5 Δ32/Δ32 aHSCT that confers resistance to CCR5 tropic HIV infection. This resulted in ART-free HIV remission for up to 12 years in the pioneer success case (the first Berlin patient) and for over 5 years in the London and Dusseldorf patients.

Transplants without the Δ32 mutation are reportedly unable to confer HIV remission beyond 9 months, until the case of the Geneva patient emerged – a male HIV patient who has been in remission for over 2 years following receipt of a CCR5 WT/WT transplant.

“When we now add the next Berlin patient [to this roster] and seeing that we are coming close to 6 years of HIV remission, I think we can quite confidently say that we can [achieve] effective HIV reservoir reduction, durable HIV remission, and a potential HIV cure with functional viral coreceptors,” said Gaebler.

“We believe that allogeneic immunity fundamentally contributes to HIV eradication,” Gaebler added. “We believe [our findings are] important because it can show that potential HIV cure can be achieved after aHSCT independent of CCR5 status.”

Implications for cure strategies

The IAS** news release noted that the next Berlin patient appears to be the first HIV remission case whose donor had a heterozygous (ie, single) rather than a homozygous (ie, double) CCR5 Δ32 mutation. [https://www.iasociety.org/news-release/worlds-seventh-hiv-cure-case-following-stem-cell-transplant-among-scientific, accessed July 30, 2024]

According to the WHO, this is “an important difference”. [https://www.who.int/news/item/25-07-2024-a-seventh-case-of-hiv-remission-reported-at-aids-2024, accessed July 30, 2024]

The WHO report notes that this “confirms the existence of several routes to explore different interventions to stimulate specific stem cells to reach long-term HIV control and cure. If patients can use SCT donors with only a single mutation in the CCR5 receptor, this potential HIV cure strategy could be more widely used, as this genetic profile is more frequently found.”

“[This case] suggests that we can broaden the donor pool for these kinds of cases, although SCT is only used in people who have another illness, such as leukaemia. This is also promising for future HIV cure strategies based on gene therapy, because it suggests that we do not have to eliminate every single piece of CCR5 to achieve remission,” said IAS President Dr Sharon Lewin from the University of Melbourne in Australia, in the IAS news release.