Resistance-Associated Mutations and Polymorphisms among Integrase Inhibitor-Naïve HIV-1 Patients in Kuwait
Affiliations
Affiliations
- Department of Microbiology, Faculty of Medicine, Kuwait University, Safat, Kuwait.
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.
Similar articles
Mikasi SG, Gichana JO, Van der Walt C, Brado D, Obasa AE, Njenda D, Messembe M, Lyonga E, Assoumou O, Cloete R, Ikomey GM, Jacobs GB.AIDS Res Hum Retroviruses. 2020 May;36(5):450-455. doi: 10.1089/AID.2019.0264. Epub 2020 Jan 13.PMID: 31830799
Acharya A, Tagny CT, Mbanya D, Fonsah JY, Nchindap E, Kenmogne L, Jihyun M, Njamnshi AK, Kanmogne GD.Int J Mol Sci. 2020 Feb 25;21(5):1553. doi: 10.3390/ijms21051553.PMID: 32106437 Free PMC article.
HIV Type 1 Integrase Natural Polymorphisms in Viral Variants Circulating in FSU Countries.
Lapovok I, Laga V, Kazennova E, Bobkova M.Curr HIV Res. 2017 Nov 23;15(5):318-326. doi: 10.2174/1570162X15666170815162052.PMID: 28814231
Characterization and structural analysis of HIV-1 integrase conservation.
Ceccherini-Silberstein F, Malet I, D'Arrigo R, Antinori A, Marcelin AG, Perno CF.AIDS Rev. 2009 Jan-Mar;11(1):17-29.PMID: 19290031 Review.
Resistance to HIV integrase inhibitors.
Mesplède T, Quashie PK, Wainberg MA.Curr Opin HIV AIDS. 2012 Sep;7(5):401-8. doi: 10.1097/COH.0b013e328356db89.PMID: 22789986 Review.
Cited by
Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting.
Chehadeh W, Albaksami O, Al-Shammari S.Antivir Chem Chemother. 2020 Jan-Dec;28:2040206620927908. doi: 10.1177/2040206620927908.PMID: 32434393 Free PMC article.
Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia.
Oroz M, Begovac J, Planinić A, Rokić F, Lunar MM, Zorec TM, Beluzić R, Korać P, Vugrek O, Poljak M, Lepej SŽ.Sci Rep. 2019 Nov 21;9(1):17307. doi: 10.1038/s41598-019-53520-8.PMID: 31754119 Free PMC article.
Mboumba Bouassa RS, Mossoro-Kpinde CD, Gody JC, Veyer D, Péré H, Matta M, Robin L, Grésenguet G, Charpentier C, Bélec L.J Antimicrob Chemother. 2019 Jul 1;74(7):2030-2038. doi: 10.1093/jac/dkz099.PMID: 30891603 Free PMC article.