Related Experiment Video
Updated: Jun 20, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor
Vici Varghese1, Rajin Shahriar, Soo-Yon Rhee
1Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. viciv@stanford.edu
Objectives:
K103N, the most common nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutation in patients with transmitted resistance and in patients receiving a failing NNRTI-containing regimen, is fully susceptible to the new NNRTI, etravirine. Therefore, we sought to determine how often NNRTI-resistant mutations other than K103N occur as minority variants in plasma samples for which standard genotypic resistance testing detects K103N alone.
Methods:
We performed ultradeep pyrosequencing (UDPS; 454 Life Sciences a Roche Company, Branford, CT) of plasma virus samples from 13 treatment-naive and 20 NNRTI-experienced patients in whom standard genotypic resistance testing revealed K103N but no other major NNRTI-resistance mutations.
Results:
Samples from 0 of 13 treatment-naive patients vs. 7 of 20 patients failing an NNRTI-containing regimen had minority variants with major etravirine-associated NNRTI-resistant mutations (P = 0.03, Fisher exact test): Y181C (7.0%), Y181C (3.6%) + G190A (3.2%), L100I (14%), L100I (32%) + 190A (5.4%), K101E (3.8%) + G190A (4.9%), K101E (4.0%) + G190S (4.8%), and G190S (3.1%).
Conclusions:
In treatment-naive patients, UDPS did not detect additional major NNRTI-resistant mutations suggesting that etravirine may be effective in patients with transmitted K103N. In NNRTI-experienced patients, UDPS often detected additional major NNRTI-resistant mutations suggesting that etravirine may not be fully active in patients with acquired K103N.
Related Concept Videos
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Antiviral Nucleoside Inhibitors
Viral Mutations
Principles of Pharmacogenetics: Types of Genetic Variants
Retrovirus Life Cycles
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

