Medicine: Sustained HIV-1 remission after stem cell transplantation

A recipient of an allogeneic hematopoietic stem cell transplant to treat leukemia has shown persistent suppression of human immunodeficiency virus type 1 (HIV-1) more than 9 years after the transplantation and 4 years after the suspension of anti-retroviral therapy. The results are reported in Nature Medicine this week.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure used to treat certain cancers, such as leukemia, by transferring immature blood cells from a donor to repopulate the bone marrow of the recipient. CCR5Δ32/Δ32 HSCT involves the transfer of cells from a donor with two copies of the Δ32 mutation in the gene encoding the HIV-1 co-receptor CCR5; such cells are resistant to HIV-1 infection. So far there have been two published cases of patients experiencing remission of HIV-1 after cancer treatment involving the transplantation of CR5Δ32/Δ32 hematopoietic stem cells: the ‘London patient’ and the ‘Berlin patient’.

Björn-Erik Jensen and colleagues now present a detailed longitudinal analysis of blood and tissue samples from a patient demonstrating remission of both leukemia and of detectable HIV-1 after transplantation of CR5Δ32/Δ32 hematopoietic stem cells. The patient, a 53-year-old male, was diagnosed as having acute myeloid leukemia in January 2011. The patient underwent transplantation of CR5Δ32/Δ32 stem cells from a female donor in February 2013, followed by chemotherapy and infusions of donor lymphocytes. After the transplantation, anti-retroviral therapy was continued, but pro-viral HIV-1 was undetectable in the patient’s blood cells. Anti-retroviral therapy was suspended in November 2018 with the patient’s informed consent, almost 6 years after the stem cell transplantation, to determine whether infectious HIV-1 persisted in the patient. The authors did not observe a resurgence of HIV-1 RNA or a boosting of the immune response to HIV-1 proteins that might have suggested a lingering, yet undetectable, viral reservoir 4 years after the suspension of anti-retroviral treatment.

The authors conclude that although HSCT remains a high-risk procedure that is at present an option only for some people living with both HIV-1 and hematological cancers, these results may inform future strategies for achieving long-term remission of HIV-1.