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Prolonged HIV-1 Remission in an Individual Treated During Hyperacute Infection
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Reported by Jules Levin
9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris
Timothy J. Henrich1*, Hiroyu Hatano2, Alison Hill3, Oliver Bacon2,4, Mary Kearney5, Joel Blankson6, Stephanie Cohen2,4, Mohamed Abdel Mohsen2,6, Remi Fromentin7, Jonathan Spindler5, Kelly Metcalf-Pate6, Robert Siliciano8,9, Douglas Richman10, Nicolas Chomont7, Janet Siliciano8, John Mellors11, Teri Liegler2, Steven Deeks2
1 Division of Experimental Medicine, UCSF; 2 Division of HIV, Infectious Diseases and Global Medicine, UCSF; 3 Program for Evolutionary Dynamics, Harvard University, Cambridge, MA; 4 San Francisco Department of Public Health; 5 HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD; 6 Center for AIDS Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; 7 Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, QC, Canada; 8 Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD; 9 Howard Hughes Medical Institute; 10 Veterans Affairs San Diego Healthcare System, CA; 11 Department of Medicine, University of Pittsburgh, Pittsburgh, PA
abstract
Background: It is unknown if extremely early initiation of ART may be curative. We describe an individual who started ART an estimated 10 days after infection with plasma HIV RNA of 220 copies/ml. After extensive blood and tissue sampling, he underwent an analytical treatment interruption (ATI) following 34 months of ART.
Methods: Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma and large numbers of PBMC obtained longitudinally were studied for HIV persistence in several laboratories using molecular and culture-based detection methods including a humanized mouse outgrowth assay.
Results: The individual initiated PrEP (TDF/FTC) during very early Fiebig stage I (HIV-1 RNA+ EIA-) followed by ART intensification (TDF/FTC/r/DRV/RAL) 8 days later. HIV RNA levels were 120 and < 40 copies/mL, 7 and 22 days after PrEP initiation, respectively, followed by no detectable level. Low-level cell-associated HIV RNA (3.2 copies/million CD4+ T cells) was detected 32 days after infection. Over the following 2 years, no further HIV could be detected, despite massive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, CD4+ T cell subsets and plasma. 530 million CD4+ T cells were also assayed in a humanized mouse outgrowth assay. One mouse (53 million input cells) experienced very low level viremia (201 copies/mL) after 5.5 weeks, but sequence confirmation was unsuccessful. The participant stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI, and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission.
Conclusions: We report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission.
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