In this case in which ART was interrupted one week before allo-HSCT, a rapid viral rebound of a pre-existing minority HIV-1 variant able to infect cells via the alternative CXCR4 co-receptor was observed three weeks later 9, 10. The only other case of an HIV-infected patient transplanted with CCR5Δ32/Δ32 cells who interrupted ART was the ‘Essen Patient’ 9. This 32-base pair deletion prevents CCR5 expression rendering these cells resistant to infection with HIV variants utilising the CCR5 co-receptor 8. Thus far, the only documented case of sustained HIV remission is the ‘Berlin Patient’, who received two allogeneic hematopoietic stem cell transplantations (allo-HSCT) using cells from a homozygous CCR5Δ32 (CCR5Δ32/Δ32) donor 1. 7 Drug-free durable HIV-1 suppression is therefore an urgent global priority. 3 Although over 21 million are accessing lifelong antiretroviral therapy (ART) 3, drug resistant HIV in both untreated 4 and treated 5, 6 individuals is significant in low and middle-income countries and sustainability of ART programs is uncertain. The HIV-1 epidemic continues with nearly 37 million infected. Although at 18 months post-treatment interruption it is premature to conclude that this patient has been cured, these 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, and the findings further support the development of HIV remission strategies based on preventing CCR5 expression. Likewise, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation whilst Cytomegalovirus (CMV)-specific responses were detectable. CD4 T cells isolated from peripheral blood post-transplant did not express CCR5 and were only susceptible to CXCR4-tropic virus ex vivo. CCR5-tropic, but not CXCR4-tropic viruses were identified in HIV-1 DNA from CD4 T cells of the patient prior to transplant. Quantitative viral outgrowth assay from peripheral CD4 T lymphocytes shows no reactivatable virus using a total of 24 million resting CD4 T cells.
Plasma HIV-1 RNA has been undetectable at <1 copy/ml along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. HIV-1 remission has been maintained through a further 18 months. Antiretroviral therapy was interrupted 16 months after transplantation. He experienced mild gut graft versus host disease. An HIV-1-infected adult underwent allo-HSCT for Hodgkin’s Lymphoma using cells from a CCR5Δ32/Δ32 donor. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. Critically, it is unclear which treatment or patient parameters contributed to this only documented case of long term HIV remission. Total body irradiation was given with each HSCT. Termed the “Berlin Patient”, the individual underwent 2 allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukemia. HIV-1 cure remains elusive with only one reported case a decade ago 1, 2.
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