Antiretroviral-Free HIV-1 Remission and Viral Rebound After Allogeneic Stem Cell Transplantation

• DOI: 10.7326/m14-1027
• Publication Date: 2014-07-21T22:31:01Z
• Authors: Timothy J. Henrich; Emily Hanhauser; Francisco M. Marty; Michael N. Sirignano; Sheila Keating; Tzong-Hae Lee; Yvonne P. Robles; Benjamin T. Davis; Jonathan Z. Li; Andrea Heisey; Alison L. Hill; Michael P. Busch; Philippe Armand; Robert J. Soiffer; Marcus Altfeld; Daniel R. Kuritzkes
• Keywords: Male; Immunology; Clinical Sciences; Antiretroviral Therapy; HIV Infections; Regenerative Medicine; 03 medical and health sciences; Stem Cell Research - Nonembryonic - Human; Clinical Research; Antiretroviral Therapy, Highly Active; 616; Humans; Highly Active; Viral; Viremia; Intestinal Mucosa; Transplantation; 0303 health sciences; Biomedical and Clinical Sciences; Remission Induction; Hematopoietic Stem Cell Transplantation; Rectum; DNA; Stem Cell Research; Hodgkin Disease; 3. Good health; Infectious Diseases; Good Health and Well Being; Medical Microbiology; Myelodysplastic Syndromes; DNA, Viral; Public Health and Health Services; HIV-1; Sexually Transmitted Infections; HIV/AIDS; RNA; RNA, Viral; Infection

It 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.To 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.Case report with characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption.Tertiary care center.Two men with HIV with undetectable HIV-1 after allogeneic HSCT for hematologic tumors.Quantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption.No 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.The study involved only 2 patients.Allogeneic 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.Foundation for AIDS Research and National Institute of Allergy and Infectious Diseases.