- New treatment strategies, based on preventing the expression of the CCR5 co-receptor, might eliminate HIV altogether.
- The HIV-1 remission in the so-called “Berlin patient”, 10 years ago, was not isolated.
- For the remission of HIV infection, a single CCR5Δ32/Δ32 allo-HSCT may be sufficient.
The only documented case of sustained HIV remission is the so-called “Berlin patient”, 10 years ago, who received 2 allo-HSCT using CCR5Δ32/Δ32 cells to treat his acute myeloid leukaemia with total body irradiation given with each HSCT. This new study reports a HIV remission with a less aggressive and toxic approach.
The HIV-1-infected adult was diagnosed in 2003, receiving antiretroviral therapy since 2012. In 2015, he received allo-HSCT for treatment of aggressive Hodgkin’s lymphoma (diagnosed in 2012), refractory to first-line chemotherapy and a number of salvage regimens. The donor was, as the “Berlin patient”, homozygous for CCR5Δ32. The 32-base pair deletion prevents CCR5 expression rendering these cells resistant to infection with HIV variants utilising the CCR5 co-receptor. As a result, host genotype was CCR5wt/wt before allo-HSCT (compared to the heterozygous CCR5WT/Δ32 genotype observed in the “Berlin Patient”), and became CCR5Δ32/Δ32 after transplant, with loss of CCR5 surface expression from circulating CD4 and CD8 T cells.
Antiretroviral therapy was maintained post-HSCT and was interrupted 16 months after transplantation. HIV-1 remission has been maintained through a further 18 months. Regular plasma viral load, weekly for the first 3 months and then monthly thereafter, was performed. These tests confirmed that 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 showed no reactivatable virus using a total of 24 million resting CD4 T cells.
CD4 T cells isolated from peripheral blood post-transplant did not express CCR5. Indeed, cells were only susceptible to CXCR4-tropic virus ex vivo.
Analyses of both antibody and T cell responses were undertaken in order to further investigate the absence of persistent HIV-1 infection and antigenic stimulation. Both are highly reminiscent of observations in the “Berlin patient”.
Likewise in this study, the “Berlin patient” was CCR5-tropic HIV-1 infection and received of a CCR5Δ32/Δ32 transplant, but it was unclear which treatment or patient parameters contributed the most to HIV remission: either 2 allo-HSCT or 2 total body irradiation in conjunction with cyclophosphamide as the conditioning regimen. Although at 18 months post-treatment interruption it is premature to conclude that this patient has been cured, data suggest that single allo-HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning, in this case consisting of chemotherapy agents.