Related Experiment Video
Updated: May 8, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA
Nicolas Margot1, Nina Pennetzdorfer1, Vidula Naik1
1Clinical Virology, Gilead Sciences, Inc., Foster City, CA, USA.
Background:
Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52 weeks.
Methods:
The phenotypic susceptibility to EIs of screening samples from participants was analysed using entry assays, and susceptibility to LEN was generated. Genotypic and phenotypic resistance to LEN was evaluated for subjects with virological failure through Week 52.
Results:
Overall, viruses with resistance to EIs showed no cross-resistance to LEN, with a mean fold change from wild type close to 1.0. Of the 22 participants analysed for resistance through Week 52, 9 participants (13%) had emergence of capsid resistance mutation(s) while the remaining 13 participants (18%) had no change in the capsid sequence.
Conclusion:
The gag sequence from EI-resistant isolates did not affect LEN susceptibility. The lack of cross-resistance to LEN across ARV-resistant isolates supports the use of LEN in PWH regardless of their treatment history. During the second half-year period of the CAPELLA Study, development of LEN resistance was rare and was overall associated with functional LEN monotherapy due to either nonadherence or resistance-driven non-susceptibility to OBR.
More Related Videos
08:46Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
14:51Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
Published on: June 17, 2022
Related Concept Videos
Hepatic Drug Excretion: Influencing Factors
Dosage Regimens: Partial Pharmacokinetic Parameters
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions
Therapeutic Drug Monitoring: Affecting Factors
Pharmacokinetics: Drug–Drug Interactions
Pharmacokinetic–Pharmacodynamic Relationship: Influence of Elimination Half-Life on Effect Duration