Prolonged persistence of HIV-infected cells in tissues after allogeneic hematopoietic transplant

ABSTRACT

Background: HIV persistence during antiretroviral therapy (ART), prevents HIV eradication or control. Mechanisms responsible for HIV persistence, including in tissues, are not well understood. Here we investigated persistence of HIV-infected cells in tissues for >200 days in an individual who had successful allogeneic hematopoietic cell transplant (Allo-HCT;donor CCR5 wild-type) but developed acute lymphocytic interstitial pneumonia after COVID vaccination and expired. Method(s) Clinical and autopsy records were reviewed. HIV in tissue samples and mononuclear cells (prepared by ficoll from lung and spleen) were studied by single genome sequencing (SGS, 1.1 kb gag) and single-copy PCR for HIV DNA. Result(s) Study participant was a 38 yo man with HIV/AIDS on ART with HIV RNA<50 c/ml for >3 years who had reducedintensity conditioning, HLA-mismatched unrelated donor allo-HCT for primary refractory ALK-negative anaplastic large cell lymphoma. His course was remarkably uncomplicated100% engraftment of donor CD3 and myeloid subsets confirmed by day +42 post-HCT;100% donor cells (CD4, CD8, CD19, CD14, CD56) confirmed by day +100. Per protocol, he was off all immunosuppression on day +60, did not develop acute graft-versus-host disease (GVHD), and maintained ART with HIV RNA<20 c/ml. Immune reconstitution was robust NK, CD8, and B cells within normal range, CD4=172 cells/muL at d+100. He received SARS-CoV2 mRNAvaccine (Moderna) on days +107 and +144. On d+155, he developed dyspnea, hypoxia with acute lymphocytic interstitial pneumonia, presumed vaccinerelated, with no signs of GVHD, pulmonary infection, or lymphoma. HIV-1 RNA remained <20 except 21 c/ml noted shortly before expiring on d+207. Postmortem notable only for diffuse alveolar damage with fibrosis and a small white pulpdepleted spleen. Single copy assay detected HIV DNA in brain (thalamus, frontal lobe, midbrain), lymph node, and jejunum (1.6-16 copies/106 tissue cells) but not liver, spleen, or affected lung (<0.2 copies/106 cells). SGS revealed HIV sequences were non-identical, demonstrating multiple distinct populations of infected cells were present. Conclusion(s) HIV populations are diverse in tissues even after extensive lymphodepleting chemotherapy and allo-HCT. Complete donor engraftment in tissues, including brain, may take significantly longer than engraftment measured in peripheral blood. Eradication strategies will require evaluation of tissue compartments. Copyright © 2022 Elsevier Ltd