Sustained HIV-1 remission after heterozygous CCR5Δ32 stem cell transplantation

Area of Science:

• Immunology
• Virology
• Hematology

Background:

• HIV cure is exceptionally rare, with only six documented cases.
• Successful HIV remission typically involves allogeneic stem cell transplants (allo-SCT) for hematological cancers.
• CCR5 Δ32 mutation in donors was thought essential for HIV remission without antiretroviral therapy (ART).

Purpose of the Study:

• To investigate HIV remission in patients undergoing allo-SCT without CCR5-mediated resistance.
• To provide evidence for CCR5-independent mechanisms contributing to HIV cure.
• To report a case of sustained, treatment-free HIV remission.

Main Methods:

• A patient with HIV and acute myeloid leukemia received an HLA-matched unrelated allo-SCT from a donor with a heterozygous CCR5 wild-type/Δ32 mutation.
• ART was discontinued three years post-transplant.
• HIV reservoir analysis, including proviral DNA and replication-competent virus detection in blood and tissues, was performed.
• HIV-specific antibody and T cell responses, and antibody-dependent cellular cytotoxicity (ADCC) were assessed.

Main Results:

• The patient achieved sustained, treatment-free HIV remission for over six years post-ART discontinuation.
• No replication-competent HIV was detected in blood or intestinal tissues after allo-SCT.
• Declining HIV-specific immune responses indicated the absence of viral activity.
• High ADCC activity at transplantation may have aided HIV reservoir clearance.

Conclusions:

• Durable HIV remission is achievable after allo-SCT even without CCR5 Δ32-mediated resistance.
• CCR5-independent mechanisms play a significant role in HIV cure.
• Effective reduction of the HIV viral reservoir is crucial for successful HIV cure strategies.