Resistance-Associated Mutations and Polymorphisms among Integrase Inhibitor-Naïve HIV-1 Patients in Kuwait

Intervirology. 2017;60(4):131-137. doi: 10.1159/000484692. Epub 2017 Dec 7.

Abstract

Objectives: Resistance-associated mutations (RAMs) in the integrase of different HIV-1 subtypes were investigated in a cohort of patients never exposed to integrase strand transfer inhibitors (INSTIs).

Methods: The viral RNA was extracted from plasma samples of 53 INSTI-naïve patients, and the integrase genetic region was sequenced and analyzed for subtype assignment and drug resistance.

Results: The median viral load at sampling was 5.28 × 104 RNA copies/mL. Bayesian phylogenetic analysis showed 85% of the HIV-1 isolates were non-B subtypes, with a predominance of subtypes C (22.6%) and CRF01_AE (26.4%). A total of 52 and 110 mutations were found in the integrase region of HIV-1 B and non-B subtypes, respectively. Nonpolymorphic INSTI-RAMs were not detected in this study. However, the accessory mutation E157Q was found in 1 patient with CRF02_AG, and the polymorphic mutations L74M/I that may contribute to a reduced susceptibility to INSTIs in the presence of major mutations were observed in 6 (13.3%) patients with non-B subtypes and 1 (12.5%) patient with the B subtype. Polymorphic mutations at positions known to harbor primary and accessory RAMs were also detected in this study.

Conclusion: Our results highlight the importance of monitoring the emergence of INSTI-RAMS before and after the initiation of INSTI-based therapy.

Keywords: Drug resistance; HIV-1; Integrase; Integrase strand transfer inhibitors; Mutations.

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology
  • Drug Resistance, Viral*
  • Female
  • Follow-Up Studies
  • Genotype
  • HIV Infections / epidemiology
  • HIV Infections / virology*
  • HIV Integrase / genetics*
  • HIV Integrase Inhibitors / pharmacology
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Kuwait / epidemiology
  • Male
  • Mutation*
  • Plasma / virology
  • Prevalence
  • RNA, Viral / genetics
  • RNA, Viral / isolation & purification
  • Sequence Analysis, DNA

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • RNA, Viral
  • HIV Integrase