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Analytical treatment interruption (ATI) among African women with early ART initiation with or without VRC01 circulating at HIV acquisition: study design and early observations of viral rebound and control

Title
Analytical treatment interruption (ATI) among African women with early ART initiation with or without VRC01 circulating at HIV acquisition: study design and early observations of viral rebound and control
Presenter
Shelly Karuna
Authors
S. Karuna * (1), K. Bar (2), A. DeCamp (3), E. Rudnicki (3), P.-C. Yu (3), P. Andrew (4), C. Orrell (5), A. Takalani (6), S. Takuva (6), L. Gama (7), T.-W. Chun (8), N. Mgodi (9), S. Dadabhai (10), C.-A. Mathew (11), J. Makhema (12), P. Hunidzarira (9), F. Laher (13), M. Hosseinipour (14), R. Tressler (15), L. Soto-Torres (15), M. Cohen (16), J. Currier (17), J. Eron (18), L. Corey (1), for the HVTN 805/HPTN 093/A5390 Study Team
Institutions
(1) Fred Hutch Cancer Center, Vaccine & Infectious Disease Division, Seattle, United States, (2) University of Pennsylvania, Department of Medicine, Philadelphia, United States, (3) Fred Hutch Cancer Center, Statistical Center for HIV/AIDS Research and Prevention, Seattle, United States, (4) FHI360, Durham, United States, (5) Desmond Tutu Health Foundation, Cape Town, South Africa, (6) Hutch Centre for Research in South Africa, Johannesburg, South Africa, (7) Vaccine Research Center, NIAID, Bethesda, United States, (8) National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation, Bethesda, United States, (9) University of Zimbabwe, Clinical Trials Research Centre, Harare, Zimbabwe, (10) Johns Hopkins Research Project, Blantyre, Malawi, (11) Wits Reproductive Health Institute, Johannesburg, South Africa, (12) Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana, (13) Perinatal HIV Research Unit Vaccine Research Center, Johannesburg, South Africa, (14) University of North Carolina Project-Malawi, Lilongwe, Malawi, (15) National Institute of Allergy and Infectious Diseases, Division of AIDS, Bethesda, United States, (16) University of North Carolina, Institute for Global Health and Infectious Diseases, Chapel Hill, United States, (17) University of California, Division of Infectious Diseases, Los Angeles, United States, (18) University of North Carolina, Division of Infectious Diseases, Chapel Hill, United States

BACKGROUND: Viremia rebounds rapidly in most people living with HIV upon ART cessation. Early ART initiation is associated with ART-free virologic control, and broadly neutralizing anti-HIV-1 antibodies (bnAbs) may modulate immune responses to HIV. Durable ART-free virologic control has been observed in 20-25% of African women in some cohorts, significantly higher than in other populations. The HVTN 703/HPTN 081 AMP trial evaluated VRC01 bnAb-mediated HIV-1 prevention among African women; those who acquired HIV were linked to early ART. With African community, investigator, ethics and regulatory collaborators, an AMP ATI (HVTN 805/HPTN 093/A5390) was designed to evaluate whether early ART +/- VRC01 circulating at HIV acquisition is associated with virologic control post-ATI and to assess underlying immunologic and virologic dynamics.
METHODS: AMP ATI eligibility includes African women with an estimated HIV acquisition date within 8 weeks of receiving VRC01 or placebo in AMP, early ART initiation and '¥1 year of viral suppression. Participants complete an NNRTI switch, as needed, then stop ART and receive frequent viral load (VL) and CD4+ T-cell count monitoring. ART re-initiation criteria include CD4<250, VL>1,000 for 4 weeks without 0.5log decline, or participant/clinician request to restart ART.
RESULTS: Nine participants from South Africa, Malawi, Botswana and Zimbabwe have enrolled, thus far; 7/9 met ART re-initiation criteria (n=5 for VL; n=2 for participant/clinician request). One participant requesting ART re-initiation had tenofovir levels consistent with ART use during ATI. Median time to confirmed VL>200 was 7.3 weeks (range 2.7-20.9+). Median time to meet virologic ART re-initiation criteria was 17.1 weeks (11-21.3). ART was reinitiated a median of 7 days later; all re-suppressed. No SAEs or Grade '¥2 related AEs were reported. See Figure 1.


CONCLUSIONS: In a safe and well-tolerated ongoing ATI developed with local stakeholder engagement, African women with early ART initiation +/- prior VRC01 exhibit evidence of viral rebound and control.

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