Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations

the EuResist Network Study Group, Ana B. Abecasis

Research output: Contribution to journalArticlepeer-review

Abstract

Ritonavir‐boosted atazanavir is an option for second‐line therapy in low‐ and middle-income countries (LMICs). We analyzed publicly available HIV‐1 protease sequences from previ-ously PI‐naïve patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 published studies and 757 from datasets assembled for this analysis. A total of 63% of patients received boosted atazanavir. A total of 38% had non‐subtype B viruses. A total of 264 (18%) sequences had a PI drug‐resistance mutation (DRM) defined as having a Stanford HIV Drug Resistance Database mutation penalty score. Among sequences with a DRM, nine major DRMs had a prevalence >5%: I50L (34%), M46I (33%), V82A (22%), L90M (19%), I54V (16%), N88S (10%), M46L (8%), V32I (6%), and I84V (6%). Common accessory DRMs were L33F (21%), Q58E (16%), K20T (14%), G73S (12%), L10F (10%), F53L (10%), K43T (9%), and L24I (6%). A novel nonpolymorphic mutation, L89T occurred in 8.4% of non‐subtype B, but in only 0.4% of subtype B sequences. The 264 sequences included 3 (1.1%) interpreted as causing high‐level, 14 (5.3%) as causing intermediate, and 27 (10.2%) as causing low‐level darunavir re-sistance. Atazanavir selects for nine major and eight accessory DRMs, and one novel nonpolymor-phic mutation occurring primarily in non‐B sequences. Atazanavir‐selected mutations confer low-levels of darunavir cross resistance. Clinical studies, however, are required to determine the optimal boosted PI to use for second‐line and potentially later line therapy in LMICs.

Original languageEnglish
Article number546
JournalPathogens
Volume11
Issue number5
DOIs
Publication statusPublished - May 2022

Keywords

  • antiviral therapy
  • ataza-navir
  • drug resistance
  • HIV‐1
  • mutation
  • protease
  • protease inhibitor

Fingerprint

Dive into the research topics of 'Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations'. Together they form a unique fingerprint.

Cite this