Hyperacute Infection Timothy Henrich Hiroyu Hatano Alison Hill Oliver Bacon Mary Kearney Joel Blankson Stephanie Cohen Mohamed Abdel Mohsen Remi Fromentin Jonathan ID: 914618
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Prolonged HIV-1 Remission and Viral Rebound in an Individual Treated During Hyperacute Infection
Timothy Henrich, Hiroyu Hatano, Alison Hill, Oliver Bacon, Mary Kearney, Joel Blankson, Stephanie Cohen, Mohamed Abdel Mohsen, Remi Fromentin, Jonathan Spindler, Kelly Metcalf-Pate, Robert Siliciano, Douglas Richman, Nicolas Chomont, Janet Siliciano, John Mellors, Teri Liegler, Steven Deeks
Slide2Impact of extremely early ART initiation on HIV persistence is poorly understoodScreening of high risk individuals in PrEP
program for acute infectionFocus on those starting ART during very early Fiebig stage I of infection (“hyperacute”)Participants started PrEP if rapid Ab and Ab/Ag assays negative (viral load pending)Introduction and Approach
Slide3Longitudinal sampling of c
olorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma and large numbers of PBMC; murine VOAApproach
Slide4Participant A: Started PrEP 10 days after infection: HIV plasma RNA = 220 c/
mL4th gen EIA & rapid HIV-antibody tests negativeConverted to 4-drug ART once viral load resultedNo detectable HIV in blood or tissue following suppressive ART3.2
Slide5Participant A: Started PrEP 10 days after infection: HIV plasma RNA = 220 c/
mL4th gen EIA & rapid HIV-antibody tests negativeConverted to 4-drug ART once viral load resultedNo detectable HIV in blood or tissue following suppressive ART3.2
Metcalf et a. 2015
Unable to verify result
with sequencing
Slide6Participant B: Started PrEP 12 days after infection: HIV plasma RNA = 359 c/
mL4th gen EIA & rapid HIV-antibody tests, Ab/Ag combo negativeVL rose to 3,343 copies/mL 9 days after PrEPIntermittent low-level HIV detection following suppressive ART
Slide7Participant A: Underwent ATI after 34 months of ART
No detectable HIV-1 plasma RNA or CD4+ T cell DNA or RNACD4+ T Cell Count
600
Slide8Participant A:
Underwent ATI after 34 months of ART
Slide9Estimates of
HIVReservoir Size95% probability that the reservoir <0.0057 or <0.0020 IUPM prior to ATILatent reservoir size ≈200 cells prior to ATI≈1% of individuals with a similar HIV burden may achieve lifelong ART-free remission Early ART Restricts HIV Diversity
Slide10HIV relapsed despite initiation of ART at one of the earliest possible stages of infection
Near complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remissionVery small numbers of infected cells following very early ART may prolong ART-free remissionSummary
Slide11Funding Sources:
amfAR Institute for HIV Cure Research (amfAR 109301), the Delaney AIDS Research Enterprise (DARE; AI096109 and A127966), NIH-NIAID R33 (AI116205; TJH), and NIH-NIAID (AI098480; TJH). The SCOPE cohort was also supported by the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), and by NIH ORIP (K01 OD018244, KMP), R01AI120024 (JNB), and 1R01DK108349-01 (SAY). This research was also supported by the Collaboratory for AIDS Research on Eradication (CARE; U19 AI096113 and 1UM1AI126619), the BEAT-HIV Delaney Collaboratory (1UM1Al126620), the UCSD CFAR (AI306214), the Department of Veterans Affairs, (1 IK2CX000520-01, SAY), the James B. Pendleton Charitable Trust, intramural funding to the National Cancer Institute, and by Leidos Biomedical Research, Inc. subcontract 12XS547 (JWM).