Integrase Strand Transfer Inhibitor (INSTI) Genotypic Resistance Analysis in Treatment-Naive, INSTI Free Antiretroviral-Experienced and INSTI-Experienced Turkish Patients Infected with HIV-1

SAYAN M., Yildirim F. S., AKHAN S., Karaoglan I., AKALIN E. H.

CURRENT HIV RESEARCH, cilt.20, sa.2, ss.184-192, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 20 Sayı: 2
  • Basım Tarihi: 2022
  • Doi Numarası: 10.2174/1570162x20666220303104509
  • Dergi Adı: CURRENT HIV RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.184-192
  • Anahtar Kelimeler: HIV, drug resistance, INSTI, raltegravir, elvitegravir, dolutegravir, SINGLE-TABLET REGIMEN, HIV-1-INFECTED PATIENTS, CROSS-RESISTANCE, RALTEGRAVIR, DOLUTEGRAVIR, ELVITEGRAVIR, MUTATIONS, EFFICACY, PREVALENCE, THERAPY
  • Kocaeli Üniversitesi Adresli: Evet

Özet

Background and Objective: Integrase strand transfer inhibitors (INSTIs) are currently the standard of practice for first-line HIV therapy for most patients. We evaluated the mutations associated with INSTI resistance in naive HIV-1 infected patients and treated them with antiretrovirals (ART). Methods: The study, conducted in the 2018 - 2020 period, included 50 ART-naive patients, 69 INSTI free ART-experienced patients, and 82 INSTI-experienced patients. INSTI resistance mutations were interpreted using the Stanford University HIVdb Program algorithm. Results: INSTI resistance was not detected in ART naive patients. At least one INSTI resistance mutation was detected in 10% of the INSTI-free patients and 29% of the INSTI-treated patients. Major INSTI-mutations E138K, Y143R, S147G, Q148R, N155H, and E157Q were found in raltegravir. Additional mutations, E92Q, E138K, G140A, S147G, and Q148R were found in elvitegravir; E192Q, E138K/T, G140A/S, S147G, Q148H/R, N155H, E157Q were found in dolutegravir (DTG) experienced patients. According to all drug classes, drug resistance mutation prevalences were determined at the rate of 60%, 46%, and 46% in the RAL, EVG, and DTG groups, respectively. Conclusion: Our findings provide data for treatment and resistance management of INSTIs and may provide feedback for INSTIs resistance surveillance consensus-building efforts. In viral rebound under INSTI treatment, INSTI-resistant mutations follow typical INSTI resistance pathways and high resistance rates. INSTI resistance genotypic analysis should be considered before any DTG-based regimes can be initiated in the future, and reduced DTG susceptibility should be carefully monitored and investigated.