Emergent Human Immunodeficiency Virus Type 1 (HIV-1) Drug Resistance in Randomized Trials of Contemporary Antiretroviral Regimens
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.
Authors
- Paul E. Sax (ORCID: https://orcid.org/0000-0001-8434-174X)
- Josep M. Llibre (ORCID: https://orcid.org/0000-0002-7158-6753)
- Ravindra K. Gupta (ORCID: https://orcid.org/0000-0001-9751-1808)
- Thibault Mésplède (ORCID: https://orcid.org/0000-0003-0515-9128)
- Anna María Geretti (ORCID: https://orcid.org/0000-0002-3670-6588)
- Daniel R. Kuritzkes (ORCID: https://orcid.org/0000-0001-6196-5883)
- Robert W. Shafer (ORCID: https://orcid.org/0000-0003-2513-2643)
- Raquel Martín-Iguacel (ORCID: https://orcid.org/0000-0003-3543-1970)
- Diego Ripamonti (ORCID: https://orcid.org/0000-0001-6702-6668)
- Jonathan Schapiro
Institutions
- University of Rome Tor Vergata (IT)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Royal Free London NHS Foundation Trust (GB)
- University of Cambridge (GB)
- Sheba Medical Center (IL)
- Odense University Hospital (DK)
- Erasmus MC (NL)
- Ospedale Papa Giovanni XXIII (IT)
- National Hemophilia Foundation (US)
- Africa Health Research Institute (ZA)
- Badalona Serveis Assistencials (ES)
- Centre for Omic Sciences (ES)
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES)
- Fundació Lluita contra les Infeccions (ES)
- Stanford University (US)
Publication Details
- Journal
- Clinical Infectious Diseases
- Published
- 2025-09-23
- DOI
- https://doi.org/10.1093/cid/ciaf471
- Primary Topic
- HIV/AIDS drug development and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00