1. Antiretroviral-Free HIV-1 Remission and Viral Rebound After Allogeneic Stem Cell Transplantation
- Author
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Michael P. Busch, Sheila M. Keating, Daniel R. Kuritzkes, Tzong-Hae Lee, Benjamin T. Davis, Francisco M. Marty, Jonathan Z. Li, Emily Hanhauser, Michael Sirignano, Yvonne P. Robles, Marcus Altfeld, Andrea Heisey, Robert J. Soiffer, Timothy J. Henrich, Philippe Armand, and Alison L. Hill
- Subjects
Male ,Viral rebound ,medicine.medical_treatment ,Human immunodeficiency virus (HIV) ,HIV Infections ,Hematopoietic stem cell transplantation ,Regenerative Medicine ,medicine.disease_cause ,Medical and Health Sciences ,Intestinal mucosa ,Stem Cell Research - Nonembryonic - Human ,Antiretroviral Therapy, Highly Active ,Viral ,Intestinal Mucosa ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,virus diseases ,Hematology ,General Medicine ,Hodgkin Disease ,Infectious Diseases ,surgical procedures, operative ,RNA, Viral ,HIV/AIDS ,Stem cell ,Infection ,Antiretroviral Therapy ,Viremia ,Clinical Research ,General & Internal Medicine ,Genetics ,Internal Medicine ,medicine ,Humans ,Highly Active ,Transplantation ,business.industry ,Myelodysplastic syndromes ,Rectum ,DNA ,Stem Cell Research ,medicine.disease ,Good Health and Well Being ,Myelodysplastic Syndromes ,DNA, Viral ,Immunology ,HIV-1 ,RNA ,business - Abstract
BackgroundIt is unknown whether the reduction in HIV-1 reservoirs seen after allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission.ObjectiveTo characterize HIV-1 reservoirs in blood and tissues and perform analytic antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained, antiretroviral-free HIV-1 remission.DesignCase report with characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption.SettingTertiary care center.PatientsTwo men with HIV with undetectable HIV-1 after allogeneic HSCT for hematologic tumors.MeasurementsQuantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption.ResultsNo HIV-1 was detected from peripheral blood or rectal mucosa before analytic treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 and 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia within 2 weeks of the most recent negative viral load measurement and developed symptoms consistent with the acute retroviral syndrome. One patient developed new efavirenz resistance after reinitiation of antiretroviral therapy. Reinitiation of active therapy led to viral decay and resolution of symptoms in both patients.LimitationThe study involved only 2 patients.ConclusionAllogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. The definition of the nature and half-life of such reservoirs is essential to achieve durable antiretroviral-free HIV-1 remission.Primary funding sourceFoundation for AIDS Research and National Institute of Allergy and Infectious Diseases.
- Published
- 2014
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