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. 2026 Jan:160:108144.
doi: 10.1016/j.cct.2025.108144. Epub 2025 Nov 9.

Analytical treatment interruption as a tool in the evaluation of immune-mediated interventions for long-term antiretroviral-free control of HIV-1 among people with HIV

Ana Gabriela Pires Dos Santos  1 , Manal Abunimeh  2 , Beatriz Mothe  3 , Jean-Pierre Routy  4 , Jacob P Lalezari  5 , Gary I Sinclair  6 , Simiso M Sokhela  7 , Ricardo Sobhie Diaz  8 , Siegfried Schwarze  9 , Jeff Berry  10 , Sharon R Lewin  11 , Karine Dubé  12 , Preethi Krishnan  2 , Andrew Topp  2 , Sarah Gill  2 , Daniel Cohen  2
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Free article

Analytical treatment interruption as a tool in the evaluation of immune-mediated interventions for long-term antiretroviral-free control of HIV-1 among people with HIV

Ana Gabriela Pires Dos Santos et al. Contemp Clin Trials. 2026 Jan.
Free article

Abstract

Background: Immune-mediated interventions have the potential to induce long-term antiretroviral treatment (ART)-free viral suppression in people with HIV. However, in the absence of biomarkers of viral control, studies looking at immune interventions require a planned long-term analytical treatment interruption (ATI) that may bring risks to participants and challenges for data interpretation. Herein, we describe an ongoing, global, proof-of-concept, randomized, placebo-controlled, phase 2 clinical trial with a planned ATI and illustrate how those risks have been mitigated to safely evaluate the long-term durability of ART-free viral control.

Methods: The trial evaluates an immunologic combination of low-dose budigalimab and trosunilimab administered during ATI. Adults aged 18-70 with confirmed HIV-1 on stable ART with viremia below the limit of detection and CD4+ counts >500 cells/mL willing to undergo ATI are randomized to receive budigalimab, trosunilimab, both (at 2 different trosunilimab doses), or neither. The primary efficacy endpoint is the proportion of participants achieving viral control (HIV-1 RNA <1000 copies/mL) without restarting ART at week 24. The planned ATI duration (≤112 weeks) evaluates the durability of off-ART viral control, long-term safety, and biomarkers. Key ATI elements align with published consensus recommendations [1] while incorporating feedback from members of the global HIV community.

Conclusions: By sharing this study design, we hope to inform on the lessons learned from operationalizing a global study evaluating durable ART-free viral control, including the critical role of engaging members of the HIV community during clinical trial design to ensure the success of an ATI-inclusive study.

Keywords: Analytical treatment interruption; Antiretroviral treatment; Budigalimab; HIV community; HIV-1; People with HIV; Protocol; Trosunilimab.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Ana Gabriela Pires dos Santos, Manal Abunimeh, Preethi Krishnan, Andrew Topp, Sarah Gill, and Daniel Cohen are employees of AbbVie, and may own stock or stock options. Beatriz Mothe reports consultancy, advisory and/or speaker fees from AELIX Therapeutics, Gilead Sciences, Janssen, ViiV Healthcare, AbbVie, and MSD. Jean-Pierre Routy is a speaker and consultant for AbbVie, Gilead Sciences, Merck & Co., Moderna, and ViiV Healthcare. Jacob P. Lalezari receives financial support from Cytodyn Inc. Gary I. Sinclair discloses the following: Gilead Sciences (advisor/consultant and grant/research support), Jannsen (advisor/consultant, grant/research support, honoraria), ViiV Healthcare (advisor/consultant, grant/research support, and honoraria), Thera technologies (grant/research support, honoraria, advisor/consultant), Merck (advisor/consultant, honoraria, grant/research support), AbbVie (grant/research support, advisor/consultant). Simiso Sokhela reports honoraria for consulting or speaking at educational events from MSD, AbbVie, ViiV Healthcare, and Janssen; and research grants paid to their institution from ViiV Healthcare, Janssen, and MSD. Ricardo Sobhie Diaz is a speaker and consultant for AbbVie, Gilead Sciences, MSD, Janssen, Pfizer, and ViiV Healthcare, and has received grant research support from Gilead Sciences, MSD, and Janssen. Siegfried Schwarze is a consultant for AbbVie, Gilead Sciences, Merck & Co., and ViiV Healthcare. Jeff Berry is a consultant for AbbVie, Gilead Sciences, Merck & Co., and ViiV Healthcare. Sharon R. Lewin reports grants from National Health and Medical Research Council of Australia, the United States National Institutes of Health, amfAR, mRNA Victoria, and the Medical Research Future Fund; and personal fees from Gilead, First Health, Biotron, AbbVie, ViiV Healthcare, and Esfam. Karine Dubé is a consultant for AbbVie, Gilead Sciences, and ViiV Healthcare.

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