Related Experiment Video
Updated: May 28, 2026
05:46
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Temporal Evolution of Drug Resistance to HIV Integrase Inhibitors
Indrani Choudhuri1, Jocelyn G Olvera1,2, Avik Biswas1,3
1The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Viruses
|May 27, 2026
Summary
Drug resistance mutations (DRMs) in HIV-1 integrase (IN) emerge over time, with some appearing rapidly and others slowly, impacting treatment efficacy. Understanding these timelines helps interpret resistance and guide therapy for people living with HIV/AIDS.
Area of Science:
- Virology
- Computational Biology
- Pharmacology
Background:
- HIV-1 integrase strand transfer inhibitors (INSTIs) are crucial for antiretroviral therapy (ART).
- Drug resistance mutations (DRMs) in HIV-1 integrase can reduce INSTI efficacy.
- Systematic integration of DRM emergence timelines is lacking.
Purpose of the Study:
- To synthesize evidence on the temporal evolution of HIV-1 integrase DRMs.
- To compare in vivo and in vitro DRM emergence timelines with computational predictions.
- To identify kinetic classes of DRM emergence.
Main Methods:
- Review of mutational kinetic data from people living with HIV/AIDS (PLWH) and in vitro experiments.
- Comparison with computational predictions using Potts-based fitness landscapes and kinetic Monte Carlo simulations.
- Analysis of DRM emergence, accumulation, and consolidation patterns.
Main Results:
- Identified distinct kinetic classes for fast-, intermediate-, and slow-emerging DRMs.
- Rapid DRMs (e.g., E92Q, N155H) emerge early; clinically significant DRMs (e.g., Q148H/K/R) emerge later with compensatory mutations.
- Consistent temporal trends across datasets suggest underlying epistatic constraints shape resistance evolution.
Conclusions:
- Understanding DRM timelines provides a framework for interpreting resistance at virological failure.
- Knowledge of DRM kinetics can inform optimal timing for resistance testing.
- Identifying high-risk evolutionary trajectories may precede durable resistance, aiding early intervention.
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