Resistance to integrase inhibitors: a national study in HIV -1-infected treatment-naive and -experienced patients - Groupe VIH et Virus Humains Persistants / HIV and Human Persistent Virus Group (IBS-HIV&HPV) Access content directly
Journal Articles Journal of Antimicrobial Chemotherapy Year : 2019

Resistance to integrase inhibitors: a national study in HIV -1-infected treatment-naive and -experienced patients

Brigitte Montes
Helène Jeulin
Thomas Mourez
  • Function : Author
Corinne Amiel
  • Function : Author
Julia Dina
  • Function : Author
  • PersonId : 906132

Abstract

Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice. Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated. Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure. Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.
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hal-02154049 , version 1 (30-08-2022)

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Anne-Geneviève Marcelin, Maxime Grude, Charlotte Charpentier, Pantxika Bellecave, Laura Le Guen, et al.. Resistance to integrase inhibitors: a national study in HIV -1-infected treatment-naive and -experienced patients. Journal of Antimicrobial Chemotherapy, 2019, 74 (5), pp.1368-1375. ⟨10.1093/jac/dkz021⟩. ⟨hal-02154049⟩
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