A UK team has reported the second case in the world of HIV-1 remission following CCR5Δ32/Δ32 allogeneic haematopoietic stem-cell transplantation (allo-HSCT).
The case report, published in Nature, comes 10 years after the first such case, known as the 'Berlin Patient', was documented. The latest case has been termed the ‘London Patient’.
The HIV-1-infected adult underwent allo-HSCT for Hodgkin’s lymphoma using cells from a CCR5Δ32/Δ32 donor. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained through a further 18 months.
Plasma HIV-1 RNA has been undetectable, at less than 1 copy per millilitre, along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assay from peripheral CD4 T lymphocytes shows no reactivatable virus using a total of 24 million resting CD4 T cells.
CCR5-tropic, but not CXCR4-tropic viruses were identified in HIV-1 DNA from CD4 T cells of the patient prior to transplant. CD4 T cells isolated from peripheral blood post-transplant did not express CCR5 and were only susceptible to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation.
The authors say the data suggest that single allo-HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation.
They add that the findings further support the development of HIV remission strategies based on preventing CCR5 expression.