In-depth virological and immunological characterization of HIV-1 cure after CCR5 Delta 32/Delta 32 allogeneic hematopoietic stem cell transplantation

Despite scientific evidence originating from two patients published to date that CCR5 Delta 32/Delta 32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5 Delta 32/Delta 32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5 Delta 32/Delta 32 HSCT. The recipient of an allogeneic stem cell transplant from a CCR5 Delta 32/Delta 32 donor shows evidence of HIV type 1 cure, including the absence of a viral rebound over 4 years after stopping antiretroviral treatment.