Factors associated with the emergence of integrase resistance mutations in patients failing dual or triple integrase inhibitor-based regimens in a French national survey

Abstract

Background Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance. Materials and methods A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm. Results Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0–0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model. Conclusions This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR.

Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study

“…[13][14][15][16][17][18] Dolutegravirresist ance data from routine health-care settings (especially in a non-subtype B HIV-1 epidemic context) were similarly unavailable for sub-Saharan Africa. 8,14,19 To assess Malawi's national TLD-transitioning programme, we conducted a prospective observational study to assess viral load and HIV drug resistance for 1 year following transition to TLD without previous viral load testing. Therapeutic monitoring of antiretroviral plasma concentrations was used to better understand viral failure, and retrospective assessment of viral load and HIV drug resistance at the start of the TLD regimen mimicked the transition without viral load testing approach, adding to the extremely scarce evidence base in this area.…”

Emergence of the G118R Pan-Integrase Resistance Mutation as a Result of Low Compliance to a Dolutegravir-Based cART

“…Unlike the Q148H/R/K pathway, the G118R mutation alone confers high-level resistance, and is associated with a significant reduction of HIV replication capacity [ 5 , 6 , 7 ]. G118R is rarely observed; in a study of 1100 patients failing a INSTI-based regimen in France, it was not reported [ 8 ]. It has only been reported in a handful of cases failing dolutegravir [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ], mostly non-B subtypes.…”