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The 'City of Hope' Patient: prolonged HIV-1 remission without antiretrovirals (ART) after allogeneic hematopoietic stem cell transplantation (aHCT) of CCR5-Î?32/Î?32 donor cells for acute myelogenous leukemia (AML)

Title
The 'City of Hope' Patient: prolonged HIV-1 remission without antiretrovirals (ART) after allogeneic hematopoietic stem cell transplantation (aHCT) of CCR5-Î?32/Î?32 donor cells for acute myelogenous leukemia (AML)
Presenter
Jana Dickter
Authors
J. Dickter * (1), S. Weibel (2), A. Cardoso (3), S. Li (3), K. Gendzekhadze (4), Y. Feng (5), S. Dadwal (1), R. Taplitz (1), J. Ross (6), A. Aribi (4), R. Stan (7), T. Kidambi (1), L. Lai (8), S. Chang (9), A. Chaillon (2), M. Al Malki (4), J. Alvarnas (4), S. Forman (4), J. Zaia (3)
Institutions
(1) City of Hope, Medicine, Duarte, United States, (2) University of California, San Diego, Medicine, La Jolla, United States, (3) City of Hope, Center for Gene Therapy, Duarte, United States, (4) City of Hope, Hematology and Hematopoietic Cell Transplantation, Duarte, United States, (5) City of Hope, Medical Oncology and Therapeutics Research, Duarte, United States, (6) City of Hope, Department of Pharmacy Services, Duarte, United States, (7) City of Hope, Translational Development Center, Duarte, United States, (8) City of Hope, Surgery, Duarte, United States, (9) City of Hope, Pathology, Duarte, United States

BACKGROUND: HIV-1 remission has been described post aHCT. We report a 66-year-old Caucasian male, diagnosed with HIV-1 in 1988 (CD4 nadir <100 cells/uL), undetectable HIV-1 viral load on ART since 1990s. In 2018, he developed AML, treated with chemotherapy followed by aHCT from unrelated HLA-matched CCR5-Î?32 homozygous donor. He continued emtricitabine/tenofovir alafenamide/dolutegravir 25 months (m) post-aHCT. After analytic treatment interruption (ATI), he remains in HIV-1 remission.
METHODS: 3/2019-current, City of Hope.
Pre-aHCT: HIV-1 DNA quantification, sequencing of genotypic tropism. Post-aHCT: blood, intestinal biopsies were obtained for cellular HIV DNA, RNA (by droplet digital PCR); compartmental testing for donor cells; ART levels; HIV-1 antibody quantification; peripheral blood mononuclear cells (PBMC) challenged with HIV-1; HIV, CMV T-cell responses.
RESULTS: Pre-aHCT: 80 HIV-1 DNA copies/million PBMC, majority R5 tropic virus (10% false-positive rate). Post-aHCT, 14m post-ATI: 100% donor chimerism.
Post-aHCT: HIV-1 RNA undetectable (< 20 copies/mL), sporadic (low-level) detectable cellular HIV-1 DNA, RNA in PBMC, gut tissue:

Date post-aHCT months (m)RNA: msTatRev copies/1 million CD4+ T cellsRNA: skGag copies/1 million CD4+ T cellsDNA: skGag copies/1 million CD4+ T cells
+ 2m PBMC0350.00
+ 3 months PBMC000.00
+ 6m PBMC
Gut biopsy
000.00
4.22
+ 10m PBMC11.400.00
+ 13m PBMC
Gut biopsy		000.00
0.00
+18m PBMC21.900.00
+ 24m PBMC000.00
+ 30m PBMC
(5 months post-ATI)		000.00
+ 37m PBMC
Gut biopsy
(12m post-ATI)		000.00
0.00

ART levels unremarkable at 7m, 12m post-ATI. We observed declining HIV-1 specific humoral, no detectable HIV-specific cellular immune response. Participant''s CD8-depleted PBMC remained uninfected after ex vivo challenge with HIV R5 strains. Immunological studies 37m post-aHCT, 12m post-ATI: viral recall antigen analysis showed robust response to CMV stimulation, no response to HIV (CD4, CD8 T-cells).


CONCLUSIONS: We report an individual with HIV-1 transplanted for AML with CCR5-Î?32/Î?32 donor cells who at 14m post-ATI, 39m post-aHCT, has no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA. HIV cure is feasible post-aHCT as described here and in previously described reports.