The Journal of antimicrobial chemotherapy · 2026
Baseline resistance mutations and virological response to dolutegravir in treatment-naïve patients: a multicentre NGS study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Inciarte Alexy, Berrocal Leire, Santos José R, Aleman Maria R, Curran Adrian, Medina Gonzalez Rafael, Bernal Samuel, de Lazzari Elisa, Garcia Del Toro Miguel, Raventós Berta, Lopez Lirola Ana M, Martínez Esteban, Paredes Roger, Blanco José Luis, Integrasa Marginal Study Group Team Group
Аннотация
OBJECTIVES: To assess the prevalence of transmitted drug resistance mutations (TDRMs) and the impact of pre-existing resistance mutations, including minority variants, on virological response in ART-naïve individuals initiating dolutegravir-based triple therapy using next-generation sequencing (GRT-NGS).
METHODS: A multicentre, retrospective cohort study was conducted including ART-naïve individuals who started a dolutegravir-3DR between 2015 and 2019. Baseline GRT-NGS Illumina®, covering RT, PR and IN genes identified primary (P-DRM) and secondary/polymorphic (S/p-DRM) mutations in high-abundance drug resistance variants (HA-DRVs; ≥20%) and low-abundance drug resistance variants (LA-DRVs; 1%-19%). Virological failure (VF) was defined as two consecutive HIV-1 RNA ≥ 50 copies/mL. Virological response was assessed at Weeks 48 and 96.
RESULTS: Of 326 participants, 86% were male and 72% were MSM; 78% received DTG/ABC/3TC and 22% TDF/FTC + DTG. At least one TDRM was detected in 24% and any DRM in 48% of subjects. Virological suppression was achieved in 76% by intention-to-treat (ITT), 97% on-treatment (OT) and 56% (ITT), 94% (ITT) at Weeks 48 and 96, respectively. VF occurred in 11 subjects (3.4%), mostly within 48 weeks, all with low-level viraemia (<1000 copies/mL; 8 < 200 copies/mL) and no emergent of new DRM in HA-DRVs with phenotypic impact. Among those with pre-existing DRM, including 36 P-HA-DRVs, 79 S/p-HA-DRVs, 57 P-LA-DRVs and 45 S/P-LA-DRVs, no significant association with VF was observed.
CONCLUSIONS: Our findings indicate that pre-existing IN and RT DRM, including low-abundance and secondary/polymorphic variants, did not compromise the virological efficacy of dolutegravir-based triple therapy in ART-naïve individuals, supporting the high resistance barrier of dolutegravir and the lack of need for baseline resistance testing.
METHODS: A multicentre, retrospective cohort study was conducted including ART-naïve individuals who started a dolutegravir-3DR between 2015 and 2019. Baseline GRT-NGS Illumina®, covering RT, PR and IN genes identified primary (P-DRM) and secondary/polymorphic (S/p-DRM) mutations in high-abundance drug resistance variants (HA-DRVs; ≥20%) and low-abundance drug resistance variants (LA-DRVs; 1%-19%). Virological failure (VF) was defined as two consecutive HIV-1 RNA ≥ 50 copies/mL. Virological response was assessed at Weeks 48 and 96.
RESULTS: Of 326 participants, 86% were male and 72% were MSM; 78% received DTG/ABC/3TC and 22% TDF/FTC + DTG. At least one TDRM was detected in 24% and any DRM in 48% of subjects. Virological suppression was achieved in 76% by intention-to-treat (ITT), 97% on-treatment (OT) and 56% (ITT), 94% (ITT) at Weeks 48 and 96, respectively. VF occurred in 11 subjects (3.4%), mostly within 48 weeks, all with low-level viraemia (<1000 copies/mL; 8 < 200 copies/mL) and no emergent of new DRM in HA-DRVs with phenotypic impact. Among those with pre-existing DRM, including 36 P-HA-DRVs, 79 S/p-HA-DRVs, 57 P-LA-DRVs and 45 S/P-LA-DRVs, no significant association with VF was observed.
CONCLUSIONS: Our findings indicate that pre-existing IN and RT DRM, including low-abundance and secondary/polymorphic variants, did not compromise the virological efficacy of dolutegravir-based triple therapy in ART-naïve individuals, supporting the high resistance barrier of dolutegravir and the lack of need for baseline resistance testing.