Sustained HIV-1 remission after heterozygous CCR5Δ32 stem cell transplantation
Summary
This Nature article reports a rare and significant case of sustained, treatment-free HIV-1 remission following an allogeneic stem cell transplant (allo-SCT) where neither donor nor recipient was homozygous for the CCR5Δ32 mutation. A male living with HIV and acute myeloid leukaemia received an HLA-matched unrelated donor transplant; both donor and recipient were heterozygous for CCR5 (wild-type/Δ32). Three years after transplantation the patient stopped antiretroviral therapy (ART). More than six years later, plasma HIV RNA remains undetectable.
Pre-transplant analyses detected intact proviral HIV. After transplant, no replication-competent virus was found in blood or intestinal tissues; HIV-specific antibody and T cell responses declined or were absent, supporting a lack of ongoing viral activity. High antibody-dependent cellular cytotoxicity (ADCC) measured at transplantation may have helped clear the reservoir. The authors conclude CCR5Δ32 homozygosity is not essential for durable remission and emphasise the central role of effective reservoir reduction in cure strategies.
Key Points
- A patient with HIV and acute myeloid leukaemia underwent allo-SCT from an HLA-matched unrelated donor; both were heterozygous CCR5 wild-type/Δ32.
- ART was discontinued three years after allo-SCT; the patient has remained in remission with undetectable plasma HIV RNA for over six years.
- Intact proviral sequences were present before transplant, but no replication-competent virus was detected post-transplant in blood or intestinal tissue.
- HIV-specific antibody and T cell responses declined or became absent, consistent with lack of viral replication.
- High ADCC activity at transplantation may have contributed to reservoir clearance, indicating immune mechanisms beyond CCR5 resistance can be important.
Context and relevance
Cures of HIV have been exceedingly rare and historically linked to allo-SCT from donors homozygous for CCR5Δ32 (the Berlin patient and a small number of others). This case is important because it demonstrates a durable, treatment-free remission without CCR5Δ32 homozygosity, supporting the view that CCR5-independent mechanisms—notably profound reduction or elimination of the viral reservoir combined with immune-mediated clearance—can achieve remission.
For researchers and clinicians, the finding shifts emphasis toward strategies that reduce or eliminate reservoirs and harness immune effects (for example ADCC or graft-versus-reservoir phenomena) rather than relying solely on CCR5-targeted approaches. However, allo-SCT is only appropriate for patients requiring transplantation for malignancy and carries substantial risks; this is a proof-of-concept for mechanisms, not a general cure pathway for people living with HIV.
Author’s take (punchy)
Big deal: this case shows you don’t need the rare CCR5Δ32/Δ32 donor to get long-term, treatment-free HIV remission. It’s a reminder that wiping out or massively shrinking the reservoir — and the immune events that follow — can do the heavy lifting. Still, it’s one patient after a high-risk cancer treatment, so don’t start expecting a ready-made therapy yet. For cure science, though, it’s a compelling nudge to chase reservoir elimination and immune-mediated clearance approaches.
Why should I read this?
Quick and honest — this is proper proof that durable HIV remission can happen without the famous CCR5Δ32 homozygous donor. If you follow HIV cure research or work on reservoir/immune strategies, this saves you hours: the paper shows what to prioritise next (reservoir reduction + immune clearance), and why CCR5-only thinking is too narrow. Also, it’s an intriguing clinical data point for anyone tracking translational breakthroughs.