Integrase Strand Transfer Inhibitors (INSTIs) Resistance Mutations in HIV-1 Infected Turkish Patients

HIV Clin Trials. 2016 May;17(3):109-13. doi: 10.1080/15284336.2016.1153303. Epub 2016 Mar 15.

Abstract

Objectives: Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome into the host DNA. The aim of this study was to evaluate for the first time INSTI resistance mutations in Turkish patients.

Methods: This study was conducted in Turkey, between April 2013 and April 2015 using 169 HIV-1-infected patients (78 ARV naive patients and 91 ARV-experienced patients). Laboratory and clinical characteristics of ARV naive and ARV-experienced patients were as follows: gender (M/F): 71/7 and 80/11, median age: 38 and 38.4; median CD4(+) T-cell: 236 and 216 cells/mm(3), median HIV-1 RNA: 4.95+E5 and 1.08E+6 copies/ml. Population-based seqeunces of the reverse transcriptase, protease, and integrase domains of the HIV-1 pol gene were used to detect HIV-1 drug resistance mutations.

Result: INSTI resistance mutations were not found in recently diagnosed HIV-1-infected patients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 - 6.6%).

Conclusions: The prevalence of INSTI resistant mutations in ART-experienced patients suggested that resistance testing must be incorporated as an integral part of HIV management with INSTI therapies.

Keywords: DNA sequencing; Dolutegravir; Drug resistance; Elvitegravir; HIV-1 integrase; Integrase inhibitors; Raltegravir.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • CD4 Lymphocyte Count
  • Codon
  • Coinfection
  • Drug Resistance, Viral*
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV Integrase Inhibitors / pharmacology
  • HIV Integrase Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation*
  • RNA, Viral
  • Risk Factors
  • Turkey
  • Viral Load
  • Young Adult

Substances

  • Codon
  • HIV Integrase Inhibitors
  • RNA, Viral