Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial

JD Gunst; JF Højen; MH Pahus; M Rosás-Umbert; B Stiksrud; JH McMahon; PW Denton; H Nielsen; IS Johansen; T Benfield; S Leth; J Gerstoft; L Østergaard; MH Schleimann; R Olesen; H Støvring; L Vibholm; N Weis; AM Dyrhol-Riise; KBH Pedersen; JSY Lau; DC Copertino; N Linden; TT Huynh; V Ramos; RB Jones; SR Lewin; M Tolstrup; TA Rasmussen; MC Nussenzweig; M Caskey; DH Reikvam; OS Søgaard

Journal article

Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial

JD Gunst, JF Højen, MH Pahus, M Rosás-Umbert, B Stiksrud, JH McMahon, PW Denton, H Nielsen, IS Johansen, T Benfield, S Leth, J Gerstoft, L Østergaard, MH Schleimann, R Olesen, H Støvring, L Vibholm, N Weis, AM Dyrhol-Riise, KBH Pedersen Show all

Nature Medicine | Published : 2023

DOI: 10.1038/s41591-023-02547-6

Abstract

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic ..

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University of Melbourne Researchers

Jillian Lau Author

Sharon Lewin Author

Thomas Rasmussen Author

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Grants

Awarded by National Institutes of Health

Funding Acknowledgements

We thank all study participants who devoted time to our research as well as every clinical research unit involved in the study. We acknowledge The Rockefeller University for providing 3BNC117 and 10-1074 and Mologen AG (now part of Gilead Sciences, Inc.) for providing lefitolimod. The funders were not involved in the study design/operations, data collection/analysis/interpretation or preparation of the manuscript. The study was funded through a Gilead HIV Cure grant to O.S.S. Study drugs were donated free of charge by The Rockefeller University (3BNC117 and 10-1074) and Mologen AG/Gilead Sciences, Inc. (lefitolimod) for use in this trial. J.D.G. is supported by the Lundbeck Foundation (R381-2021-1405). P.W.D. is supported by the National Institute of General Medical Sciences of the National Institutes of Health under award P20 GM103427. Partial support for virologic analysis was provided by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award R01AI47845 (RBJ), supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, the National Institute on Drug Abuse and the National Heart, Lung, and Blood Institute. S.R.L. is supported by funding from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award UM1AI126611-01 and the National Health and Medical Research Council (NHMRC) of Australia (1135851 and 1149990). S.R.L. is an NHMRC Practitioner Fellow. O.S.S. is also supported by the Danish Council for Independent Research (grant 9060-00023B) and the Lundbeck Foundation (R313-2019-790). None of the specific sources of funding had any role in the conceptualization, design, data collection, analysis, decision to publish or preparation of the manuscript.