1. 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

2. Introduction and Approach
Impact of extremely early ART initiation on HIV persistence is poorly understood
Screening of high risk individuals in PrEP program for acute infection
Focus 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)

3. Approach
Longitudinal sampling of colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma and large numbers of PBMC; murine VOA

4. Started PrEP 10 days after infection: HIV plasma RNA = 220 c/mL
Participant A:
Started PrEP 10 days after infection: HIV plasma RNA = 220 c/mL
4th gen EIA & rapid HIV-antibody tests negative
Converted to 4-drug ART once viral load resulted
No detectable HIV in blood or tissue following suppressive ART
3.2

5. Unable to verify result with sequencing
Participant A:
Started PrEP 10 days after infection: HIV plasma RNA = 220 c/mL
4th gen EIA & rapid HIV-antibody tests negative
Converted to 4-drug ART once viral load resulted
No detectable HIV in blood or tissue following suppressive ART
3.2
Metcalf et a. 2015
Unable to verify result with sequencing

6. Participant B:
Started PrEP 12 days after infection: HIV plasma RNA = 359 c/mL
4th gen EIA & rapid HIV-antibody tests, Ab/Ag combo negative
VL rose to 3,343 copies/mL 9 days after PrEP
Intermittent low-level HIV detection following suppressive ART

7. No detectable HIV-1 plasma RNA or CD4+ T cell DNA or RNA
Participant A:
Underwent ATI after 34 months of ART
No detectable HIV-1 plasma RNA or CD4+ T cell DNA or RNA
CD4+ T Cell Count
600

8. Participant A:
Underwent ATI after 34 months of ART

9. Estimates of HIV Reservoir Size
95% probability that the reservoir < or < IUPM prior to ATI
Latent 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

10. Summary
HIV 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 remission
Very small numbers of infected cells following very early ART may prolong ART-free remission

11. Funding Sources: amfAR Institute for HIV Cure Research (amfAR ), the Delaney AIDS Research Enterprise (DARE; AI 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), R01AI (JNB), and 1R01DK (SAY). This research was also supported by the Collaboratory for AIDS Research on Eradication (CARE; U19 AI and 1UM1AI126619), the BEAT-HIV Delaney Collaboratory (1UM1Al126620), the UCSD CFAR (AI306214), the Department of Veterans Affairs, (1 IK2CX , SAY), the James B. Pendleton Charitable Trust, intramural funding to the National Cancer Institute, and by Leidos Biomedical Research, Inc. subcontract 12XS547 (JWM).