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RESEARCH PRODUCT

Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors

Andrea De LucaAntonia BezenchekMaurizio ZazziMassimo AndreoniRossana ScutariFrancesca IncardonaVanni BorghiIlaria VicentiDomenico Di CarloClaudia AlteriValentina ZuccaroMaria Mercedes SantoroCarlo Federico PernoAndrea AntinoriAntonio Cascio

subject

Male0301 basic medicineIntegrase inhibitorHIV InfectionsHIV IntegraseQuinolonesPiperazineschemistry.chemical_compound0302 clinical medicineHIV-1 integrase resistanceImmunology and Allergy030212 general & internal medicineIntegrase inhibitorSubtype.genetic distancebiologyElvitegravirMiddle AgedQR1-502Integraseintegrase inhibitorsDolutegravirHiv 1 integraseFemaleHeterocyclic Compounds 3-Ringmedicine.drugAdultMicrobiology (medical)Settore MED/17 - Malattie InfettiveGenotypePyridones030106 microbiologyImmunologyMicrobiologysubtypeEvolution Molecular03 medical and health sciencesRaltegravir PotassiumDrug Resistance ViralOxazinesmedicineHumansIn patientHIV Integrase InhibitorsPolymorphismbusiness.industryHIV-1 integrase resistance; genetic distance; integrase inhibitors; polymorphisms; subtypeRaltegravirVirologyLogistic ModelschemistryMutationHIV-1Genotypic resistancebiology.proteinpolymorphismsbusiness

description

Abstract 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-naive patients (19 drug-naive 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-naive 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.

yearjournalcountryeditionlanguage
2020-03-01Journal of Global Antimicrobial Resistance
https://doi.org/10.1016/j.jgar.2019.07.015