Background
To date, a few cases of HIV remission after allogeneic hematopoietic stem cell transplantation (HSCT) have been reported. While most involved CCR5Δ32/Δ32 donors, there have been recent reports of remission without this mutation, suggesting that factors beyond CCR5 might be sufficient for remission. Further reports of HIV remission are crucial to understand the factors that influence the transition to donor dominance and the loss of viral reservoirs. Here, we present the Oslo patient, who is in remission 48 months after HSCT from a CCR5Δ32/Δ32 sibling donor.
Methods
We examined HIV-specific T cell responses (proliferative and cytokine responses), serum avidity, western blot, donor chimerism, quantified the HIV reservoir (CD4+ cells from blood and CD45+ cells from ileum and colon) by intact proviral DNA assay (IPDA) and proviral HIV DNA by droplet digital PCR (ddPCR), and viral outgrowth assay (qVOA) up to 24 months post analytical treatment interruption (ATI). The patient was included in IciStem 2.0 (IciS2-56).
Results
A 58-year-old male with a 14-year history of HIV-1 clade B, CCR5 tropism, and suppressed viremia underwent HSCT for myelodysplastic syndrome. The graft came from his HLA-identical brother with CCR5Δ32/Δ32, whereas the patient carried CCR5Δ32/wt. He developed severe acute graft versus host disease (GvHD) of the gut and skin and was treated with the Janus kinase inhibitor (JAKi) ruxolitinib. T-cell reconstitution was achieved within a year. Complete donor chimerism in peripheral blood was documented by day 90 and later in gut-associated lymphoid tissues (GALT). Post HSCT, plasma HIV RNA remained undetectable, and at 24 months, ATI was initiated. Twenty-four months into ATI, HIV-specific CD4+ and CD8+ T cell responses were absent, serum HIV avidity showed weak functional affinity, and western blot showed waning HIV-1-specific antibody responses. Traces of HIV DNA were found in GALT, but no intact HIV DNA was detected in blood or GALT. Importantly, no replication competent virus was detected in 65 million CD4+ T cells by qVOA.
Conclusions
We report a novel case of HIV remission after HSCT from a sibling donor, confirmed by extensive translational work-up. The donor’s CCR5Δ32/Δ32 variant likely prevented reseeding of HIV to the allograft and prolonged GvHD possibly facilitated complete donor chimerism of GALT. Like the Geneva patient, he was treated with JAKi, which may reduce viral reservoirs. The Oslo patient adds valuable evidence to understanding HIV remission after HCST.