Sustained HIV-1 remission after heterozygous CCR5Δ32 stem cell transplantation, 2025, Gaebler et al.

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Sustained HIV-1 remission after heterozygous CCR5Δ32 stem cell transplantation

Spoiler: Authors

Gaebler, Christian; Kor, Samad; Allers, Kristina; Perotti, Michela; Mwangi, David; Meixenberger, Karolin; Hanke, Kirsten; Trenkner, Timo; Kraus, Tom; Sha, Yequin; Arentowicz, Carmen; Odidika, Stanley; Grahn, Nikolai; Scheck, Rachel; Perkins, Naomi; Pardons, Marion; Igbokwe, Vanessa; Corman, Victor; Burmeister, Thomas; Blau, Olga; Sürücü, Gülüstan; Pruß, Axel; Schneider, Christian G.; Klausen, Gerd; Sauter, Jürgen; Klein, Florian; Sander, Leif E.; Hofmann, Jörg; Vuong, Lam; Bullinger, Lars; Penter, Livius; Gruell, Henning; Reeves, Daniel B.; Schommers, Philipp; Hoelzemer, Angelique; Obermeier, Martin; Blau, Igor W.; Schneider, Thomas; Penack, Olaf

Abstract​

HIV cure is exceptionally rare, documented in only six cases among the estimated 88 million individuals who have acquired HIV since the epidemic's onset1–6.
Successful cures, including the pioneering Berlin patient, are limited to individuals receiving allogeneic stem cell transplants (allo-SCT) for hematological cancers.
HIV resistance from stem cell donors with the rare homozygous CCR5 Δ32 mutation was long considered the main mechanism for HIV remission without antiretroviral therapy (ART), but recent reports highlight CCR5-independent mechanisms as important contributors to HIV cure6–8.

Here, we provide new evidence for this conceptual shift, reporting exceptionally long, treatment-free HIV remission following allo-SCT with functionally active CCR5.
A heterozygous CCR5 wild-type/Δ32 male living with HIV received allo-SCT from an HLA-matched unrelated heterozygous CCR5 wild-type/Δ32 donor as treatment for acute myeloid leukemia.
Three years after allo-SCT, the patient discontinued ART.
To date, HIV remission has been sustained for over six years with undetectable plasma HIV RNA.
Reservoir analysis revealed intact proviral HIV before transplantation, but no replication-competent virus in blood or intestinal tissues after allo-SCT.
Declining or absent HIV-specific antibody and T cell responses support the absence of viral activity.
High antibody-dependent cellular cytotoxicity (ADCC) activity at the time of transplantation may have contributed to HIV reservoir clearance.

These results demonstrate that CCR5Δ32-mediated HIV resistance is not essential for durable remission, underscoring the importance of effective viral reservoir reductions in HIV cure strategies.

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Man unexpectedly cured of HIV after stem cell transplant

A handful of people with HIV have been cured after receiving HIV-resistant stem cells – but a man who received non-resistant stem cells is also now HIV-free

www.newscientist.com

AI Simmary:

A man has become the seventh person to be HIV-free after receiving a stem cell transplant for leukaemia. He is only the second cured individual who did not receive HIV-resistant stem cells, suggesting that such resistance may not be essential.

The man received chemotherapy in 2015, then a transplant from a donor with one normal and one mutated CCR5 gene copy. He continued antiretroviral therapy (ART) until three years later, when he stopped on his own. No virus was detected afterwards, and he has remained HIV-free for more than seven years, long enough to be considered cured.

Researchers suggest that donor immune cells may eliminate the patient’s remaining original cells before HIV can infect them. However, factors such as genetic compatibility remain critical, and HIV-resistant stem cells are still preferred.

Because stem cell transplants are risky, they are unsuitable for people with HIV who do not have blood cancer. ART or preventive drugs remain safer options.