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. 2025 Sep 23:ciaf471.
doi: 10.1093/cid/ciaf471. Online ahead of print.

Emergent Human Immunodeficiency Virus Type 1 (HIV-1) Drug Resistance in Randomized Trials of Contemporary Antiretroviral Regimens

Josep M Llibre  1   2 , Diego Ripamonti  3 , Anna M Geretti  4   5 , Raquel Martin-Iguacel  6   7 , Paul E Sax  8 , Ravindra K Gupta  9   10 , Robert W Shafer  11 , Jonathan M Schapiro  12 , Daniel R Kuritzkes  8 , Thibault Mesplède  13
Affiliations

Emergent Human Immunodeficiency Virus Type 1 (HIV-1) Drug Resistance in Randomized Trials of Contemporary Antiretroviral Regimens

Josep M Llibre et al. Clin Infect Dis. .

Abstract

The occurrence of virological failure in a subset of individuals is an inevitable aspect of antiretroviral treatment, and historically has been primarily influenced by suboptimal adherence to oral therapies. The risk of selecting 1- or 2-class human immunodeficiency virus (HIV) drug resistance is influenced by the composition of the regimen, differing significantly depending on the intrinsic barrier to resistance of the regimen. HIV resistance emergence during treatment can be viewed as a regimen-related adverse effect that warrants equal consideration in clinical trials alongside virological and safety endpoints. Antiretroviral regimens demonstrating non-inferiority and showing similar rates of virological failure can nonetheless differ in terms of HIV emergent resistance. We propose the development of a systematic framework to categorize emergent HIV drug resistance in clinical trials. Standardizing the evaluation of resistance in clinical trials and its reporting to regulatory agencies will facilitate an improved understanding of regimen-specific resistance risks and better inform clinical decision making.

Keywords: HIV resistance; bictegravir; cabotegravir; dolutegravir; doravirine; drug resistance mutations; integrase inhibitors; virological failure.

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Conflict of interest statement

Potential conflicts of interest. J. M. L. has received honoraria for educational presentations, for expert testimony and support for meetings from ViiV Healthcare and Gilead Sciences. D. R. has received honoraria for educational presentations, for expert testimony and support for meetings from ViiV Healthcare, Merck and Gilead Sciences. A. M. G. has received personal honoraria from Abbott, Gilead Sciences, GSK, MSD, Roche, and ViiV Healthcare and research funding (to the institution) from Gilead, Roche and ViiV Healthcare. P. E. S. holds the position of Editor-in-Chief for Clinical Infectious Diseases and has not peer reviewed or made any editorial decisions for this paper and received research grants and consulting fees from Gilead and ViiV, and consulting fees from Merck. R. K. G. has received honoraria for educational presentations from Gilead Sciences. R. W. S. has received speaking honoraria from Gilead Sciences and ViiV Healthcare. J. M. S. has received honoraria for educational presentations, advisory boards or consulting from Gilead, Merck, ViiV/GSK and Virology education. D. R. K. has received honoraria for educational presentations, for expert testimony and/or consulting from ViiV Healthcare, Merck, Janssen, GlaxoSmithKline and Gilead Sciences. R. K. G. has received honoraria for educational presentations from Gilead Sciences. T. M. has received honoraria from ViiV Healthcare, Merck, and Gilead Sciences and a research grant from ViiV Healthcare paid to his institution. All other authors report no potential conflicts.

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