Surveillance of transmitted drug resistance to integrase inhibitors in Spain: implications for clinical practice

Álvarez, Marta; Casas, Paz; Salazar, Adolfo de; Chueca, Natalia; Guerrero-Beltrán, Carlos Enrique; Rodrı́guez, Carmen; Imaz, Arkaitz; Espinosa, Núria; García‐Bujalance, Silvia; Pérez-Elías, María Jesús; García–Álvarez, Mónica; Iribarren, José Antonio; Santos, Jesús; Dalmau, David; Aguilera, Antonio; Vinuesa, David; Gutiérrez, Félix; Piérola, Beatriz; Molina, J M; Peraire, Joaquim; Portilla, Irene; Gómez-Sirvent, Juan Luís; Olalla, Julián; Galera, Carlos; Blanco, José Ramón; Riera, Melchor; García‐Fraile, Lucio; Navarro, Gemma; Curran, Adrían; Poveda, Eva; García, Féderico; CoRIS,

doi:10.1093/jac/dkz067

Cited by 20 publications

(23 citation statements)

References 31 publications

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“…Beyond treatment efficacy, even though integrase GRT is still not strongly recommended in cART-naïve patients [5], it should be considered that in the present study, integrase baseline GRT was performed in > 70 % of the cART-naïve patients included. Based on the information retrieved from IN genotyping, we confirmed that INI resistance in cART-naïve patients is still not a concern in Italian clinical practice due to the low prevalence of both INI-MRMs (< 1 %) and INI ARMs (5 %), as observed in several studies [14,15,28]. Moreover, by evaluating virological response in the few patients harbouring baseline ARMs, we found that these mutations had no effect in achieving and/or maintaining VS in our population.…”

Section: Discussionsupporting

confidence: 80%

“…Another important point to consider is the INI-resistance. In this regard, despite the current common usage of INIs in clinical practice, mutations associated with resistance to INIs were at the moment rarely detected in INI-naïve patients (both for patients starting INI as drugnaïve or drug-experienced); and so far, the prevalence of INI transmitted resistance is still not a concern in cART naïve patients [14,15]. However, natural polymorphisms with varying effect on INI susceptibility in the absence of specific primary mutations were already described in some studies [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings

Armenia

Bouba

Gagliardini

et al. 2020

Journal of Clinical Virology

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings

Armenia

Bouba

Gagliardini

et al. 2020

Journal of Clinical Virology

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“…Between 2006 and 2007, the European SPREAD programme revealed no resistance mutations to any of INIs, although potentially relevant polymorphisms could be observed before the introduction of integrase inhibitors [15]. A possible outcome of increasing role of INIs in ART worldwide is, however, the emergence of primary integrase resistance mutations among untreated patients as observed in our study and in different European countries [16][17][18][19][20][21].…”

Section: Discussionsupporting

confidence: 50%

“…These highly or minimally polymorphic mutations occur in less than 10% of viruses from ART-naive patients depending on HIV subtype [22]. The majority of detected accessory integrase mutations in Hungary were also observed in different proportion in Austria [18], Poland [23], Spain [16], Scotland [17], Switzerland [20], UK [24] and Italy [21]. Prevalence of major and accessory integrase resistance mutations occurring in different studies is not easily comparable because of different time periods, sampling strategies, mutation identifying methodologies and datasets.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of resistance mutations associated with integrase inhibitors in therapy-naive HIV-positive patients in Hungary

Ay¹,

Pocskay²,

Lakatos

et al. 2021

AMicr

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Widespread introduction of HIV integrase inhibitors into clinical care may result in appearance of drug resistance mutations affecting treatment outcome. The aim of our study was to monitor the resistance patterns of integrase inhibitors beside protease and reverse transcriptase inhibitors in newly diagnosed therapy-naive HIV-positive patients in Hungary between 2017 and 2019.Genotype-based resistance testing of HIV integrase, protease and reverse transcriptase was performed by amplification and Sanger population sequencing from plasma samples. Drug resistance mutations were identified by the algorithm of Stanford HIV Drug Resistance Database.Potentially transmitted, non-polymorphic integrase major mutation was detected in 1 out of 249 samples, while accessory mutations were observed in further 31 patients (12.4%). The overall prevalence of transmitted drug resistance (TDR) mutations related to protease and reverse transcriptase inhibitors was 5.8% (10/173) between the end of 2017 and 2019. Nucleoside reverse transcriptase inhibitor associated resistance mutations were the most frequent indicators of TDR (6/173; 3.5%), followed by resistance mutations associated with protease (3/173; 1.7%) and non-nucleoside reverse transcriptase inhibitors (2/173, 1.2%).The first detection of integrase major mutation and the changing patterns of other resistance mutations in Hungarian untreated HIV-positive population indicate the necessity of continuous molecular surveillance of Hungarian HIV epidemic.

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“…During the early stages of the development of the test-and-treat strategy, concerns arose whether not having a resistance test could increase the risk for virological failure if one drug was not fully active against HIV. However, the prevalence of baseline HIV mutations compromising INSTI efficacy is very low [66,67]. In addition, baseline M184V mutation is very uncommon, according to several studies [25,[68][69][70].…”

Section: Test-and-treat Scenariosmentioning

confidence: 99%

Two-Drug Regimens for HIV—Current Evidence, Research Gaps and Future Challenges

et al. 2022

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During the last 30 years, antiretroviral treatment (ART) for human immunodeficiency virus (HIV) infection has been continuously evolving. Since 1996, three-drug regimens (3DR) have been standard-of-care for HIV treatment and are based on a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The effectiveness of first-generation 3DRs allowed a dramatic increase in the life expectancy of HIV-infected patients, although it was associated with several side effects and ART-related toxicities. The development of novel two-drug regimens (2DRs) started in the mid-2000s in order to minimize side effects, reduce drug–drug interactions and improve treatment compliance. Several clinical trials compared 2DRs and 3DRs in treatment-naïve and treatment-experienced patients and showed the non-inferiority of 2DRs in terms of efficacy, which led to 2DRs being used as first-line treatment in several clinical scenarios, according to HIV clinical guidelines. In this review, we summarize the current evidence, research gaps and future prospects of 2DRs.

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Surveillance of transmitted drug resistance to integrase inhibitors in Spain: implications for clinical practice

Cited by 20 publications

References 31 publications

Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings

Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings

Prevalence of resistance mutations associated with integrase inhibitors in therapy-naive HIV-positive patients in Hungary

Two-Drug Regimens for HIV—Current Evidence, Research Gaps and Future Challenges

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