HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK

On behalf of the UK HIV Drug Resistance Database (UKHDRD), The UK Collaborative HIV Cohort (UK CHIC) Study Steering Committees

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Background: Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. Objectives: We examined darunavir DRMs emerging in clinical practice in the UK. Patients and methods: Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PInaive controls. Results: Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. Conclusions: Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility.

Original languageEnglish
Pages (from-to)3487-3494
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Issue number12
Publication statusPublished - Dec 2016

Bibliographical note

Publisher Copyright:
© The Author 2016.


Dive into the research topics of 'HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK'. Together they form a unique fingerprint.

Cite this