Plasma Viremia and Cellular HIV-1 DNA Persist Despite Autologous Hematopoietic Stem Cell Transplantation for AIDS-related Lymphoma
Anthony Cillo*1, A Krishnan2, R Mitsuyasu3, D McMahon1, S Li2, J Rossi2, J Zaia2, and J Mellors1
1Univ of Pittsburgh, PA, US; 2City of Hope Natl Med Ctr, Duarte, CA, US; and 3Univ of California, Los Angeles, US
Background: Allogeneic hematopoietic stem cell transplantation with stem cells derived from a CCR5∆32 homozygous donor achieved a drug-free cure of HIV infection in one individual. It is not known which component(s) of the patient’s therapy were necessary to achieve a cure. We therefore examined the effects of intensive myeloablative chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) on HIV-1 persistence.
Methods: A multicenter cross-sectional study of AIDS-related lymphoma patients who underwent ASCT and had plasma HIV-1 RNA suppressed to <50 copies/mL on ART was conducted. HIV-1 RNA from plasma, total HIV-1 DNA, and 2-LTR circles from peripheral blood mononuclear cells (PBMC) were measured using single-copy qPCR assays. HIV-1– control plasma and PBMC were run in parallel with all patient samples.
Results: A total of 10 patients (6 from City of Hope; 3 from UCLA; 1 from U Pitt) were studied. Clinical characteristics, HIV-1 RNA from plasma, total HIV-1 DNA, and 2-LTR circles from PBMC post-ASCT are shown below. Persistent viremia was detected in 9 of 10 patients post-SCT, with a median HIV-1 RNA of 1.5 copies/mL (range: <0.2 to 26). Similarly, HIV-1 DNA was detectable post-ASCT in 9 of 10 patients, with a median total HIV-1 DNA of 554 copies/106 PBMC (range: <0.4 to 2179). 2-LTR circles were detectable post-ASCT in only 2 of 10 patients (range: 1 to 7 copies/106 PBMC). Notably, the only patient with undetectable plasma HIV-1 RNA had the highest levels of HIV-1 DNA and 2-LTR circles. Additionally, plasma viremia persisted in a patient with undetectable HIV-1 DNA in PBMC.
Conclusions: HIV-1 reservoirs including low-level viremia persist following myeloablative chemotherapy and autologous stem cell transplantation. These findings suggest that allogeneic stem cell transplantation with CCR5 defective donor cells was critical in achieving the reported cure of HIV.