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TWO HUNDRED EIGHTY-EIGHT–DAY DRUG-FREE REMISSION FROM HIV REBOUND BY ALLOGENEIC PBSCT
Nathan Cummins1, Stacey Rizza1, Jason Baker2, Nicolas Chomont3, Tae-Wook Chun4, Mathias Lichterfeld5, Douglas D. Richman6, Timothy Schacker7, Joseph D. Yao1, Andrew Badley1
1Mayo Clinic, Rochester, MN, USA,2Univ of Minnesota, Minneapolis, MN, USA,3Univ de Montréal, Montreal, QC, Canada,4NIH, Bethesda, MD, USA,5Massachusetts General Hosp, Boston, MA, USA,6Univ of California San Diego, La Jolla, CA, USA,7Univ of Minnesota, Minneapolis, MN, USA
As HIV cure strategies are tested a reliable measure of cure is needed to predict drug-free remission from viral rebound. We evaluated HIV reservoir size through the post-transplant period in a patient with HIV who underwent allogeneic peripheral blood stem cell transplant (PBSCT) for acute lymphoblastic leukemia. An antiretroviral Analytic Treatment Interruption was initiated after 2 years.
PBMCs were obtained by leukapheresis for HIV reservoir size estimation. Plasma was tested with Amplicor HIV-1 DNA Test, v1.5. Total HIV DNA in CD4 T cells was measured by qPCR and digital droplet PCR separately. Integrated HIV DNA in CD4 T cell subsets was measured by Alu-nested PCR. The frequency of CD4 T cells with replication competent virus was determined by quantitative viral outgrowth assay.
A 55 y.o. man with ART suppressed HIV-1 was seen at Mayo Clinic for B-cell ALL. He underwent allogeneic reduced-intensity conditioning PBSCT with an HLA- and ABO-matched sibling as donor, with tacrolimus and methotrexate for GVHD prophylaxis. Both donor and recipient were CCR5 wild-type. His course was notable for mild GVHD in colon (biopsy confirmed) and Pneumocystis jiroveci pneumonia. As of this report the ALL is in complete remission. ART was continued through the peri-transplant period, and plasma HIV-1 RNA and proviral DNA became undetectable by clinical assays. In situ hybridization for HIV in GI lymphatic tissue (colon) was negative. Table below presents results from HIV reservoir assessments. Total and integrated HIV DNA and replication competent virus in peripheral CD4 T cells decreased post-transplant to undetectable or near undetectable levels. At 784 days post PBSCT, given multiple negative tests for HIV and de-evolving western blot for antibodies to HIV, he initiated ATI of all ART. Plasma viremia was measured weekly for 8 weeks, then monthly, and remained undetectable (LLD 10 copies/ml) for 9 months post-ATI. On ATI day 288 his plasma HIV RNA level became detectable at 48 copies/ml, increased to 283 (ATI day 289), and then 1640 (ATI day 293), prompting reinitiation of ART.
Our case illustrates that PBSCT with ART can significantly reduce HIV reservoir size, and enable prolonged drug free remission from HIV rebound. It is unclear why in the absence of cure, HIV rebound was profoundly delayed at 288 days post ATI. Functional analyses are underway to identify immune mechanisms which may have delayed HIV rebound.