Exploring HIV-1 Cure Strategies: Insights from CCR5Δ32/Δ32 Allogeneic Hematopoietic Stem Cell Transplantation

Human Immunodeficiency Virus Type 1 (HIV-1) remains a major global health concern despite advances in antiretroviral therapy (ART). ART has transformed HIV-1 into a manageable chronic condition, yet it is not curative, as it does not eliminate viral reservoirs that persist and can reignite infection if treatment is discontinued. A functional cure for HIV-1—control of the virus without ongoing ART—has been a significant focus of research, particularly through approaches such as allogeneic hematopoietic stem cell transplantation (HSCT) with donors harboring the CCR5Δ32 mutation. The CCR5Δ32 mutation prevents HIV-1 from entering host cells by disrupting the CCR5 receptor, a key co-receptor for viral entry, which makes individuals resistant to CCR5-tropic strains of HIV-1. This review mainly focuses a case study of a 53-year-old male with HIV-1 and acute myeloid leukemia (AML), who received a CCR5Δ32/Δ32 HSCT in 2013. The patient exhibited long-term HIV-1 remission, with no viral rebound 48 months after stopping ART. Despite sporadic detection of HIV-1 DNA, no replication-competent virus was found through extensive virological and immunological assessments. The study suggests that the combination of CCR5Δ32/Δ32 transplantation, chemotherapy, and a graft-versus-HIV effect contributed to reducing the viral reservoir and maintaining viral suppression. In addition to other four cases with similar situation from the past, which are London case (2009), Berlin case (2013), Caucasian case (2022), and US case (2022), together supporting the potential of CCR5Δ32/Δ32 HSCT as a functional cure for HIV-1, while highlighting the need for further research to optimize this approach for broader application.