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)


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

+ 10m PBMC11.400.00
+ 13m PBMC
Gut biopsy
+18m PBMC21.900.00
+ 24m PBMC000.00
+ 30m PBMC
(5 months post-ATI)
+ 37m PBMC
Gut biopsy
(12m post-ATI)

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.