Objectives: This study evaluated the emergence of mutations associated with integrase strand transfer inhibitors (INSTI) resistance (INSTI-RMs) and the integrase evolution in human immunodeficiency virus type 1 (HIV-1) infected patients treated with this drug class. Methods: The emergence of INSTI-RMs and integrase evolution (estimated as genetic distance between integrase sequences under INSTI treatment and before INSTI treatment) were evaluated in 107 INSTI-naïve patients (19 drug-naïve and 88 drug-experienced) with two plasma genotypic resistance tests: one before INSTI treatment and one under INSTI treatment. A logistic regression analysis was performed to evaluate factors associated with the integrase evolution under INSTI treatment. Results: The patients were mainly infected by B subtype (72.0%). Eighty-seven patients were treated with raltegravir, 13 with dolutegravir and seven with elvitegravir. Before INSTI treatment one patient harboured the major INSTI-RM R263K and three patients the accessory INSTI-RMs T97A. Under INSTI treatment the emergence of ≥1 INSTI-RM was found in 39 (36.4%) patients. The major INSTI-RMs that more frequently emerged were: N155H (17.8%), G140S (8.4%), Y143R (7.5%), Q148H (6.5%), and Y143C (4.7%). Concerning integrase evolution, a higher genetic distance was found in patients with ≥1 INSTI-RM compared with those without emergence of resistance (0.024 [0.012–0.036] vs. 0.015 [0.009–0.024], P = 0.018). This higher integrase evolution was significantly associated with a longer duration of HIV-1 infection, a higher number of past regimens and non-B subtypes. Conclusions: These findings confirm that major INSTI-RMs very rarely occur in INSTI-naïve patients. Under INSTI treatment, selection of drug-resistance follows the typical drug-resistance pathways; a higher evolution characterises integrase sequences developing drug-resistance compared with those without any resistance.
Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors / R. Scutari, C. Alteri, I. Vicenti, D. Di Carlo, V. Zuccaro, F. Incardona, V. Borghi, A. Bezenchek, M. Andreoni, A. Antinori, C.F. Perno, A. Cascio, A. De Luca, M. Zazzi, M.M. Santoro. - In: JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE. - ISSN 2213-7165. - 20(2020 Mar), pp. 163-169.
|Titolo:||Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors|
|Parole Chiave:||Genetic distance; HIV-1 integrase resistance; Integrase inhibitors; Polymorphisms; Subtype|
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Data di pubblicazione:||mar-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jgar.2019.07.015|
|Appare nelle tipologie:||01 - Articolo su periodico|