Fatores associados às mutações de resistência à integrase em indivíduos iniciando a terapia antirretroviral contendo dolutegravir: coorte retrospectiva, Brasil 2017-2019.

Abstract

Introduction: The World Health Organization (WHO) recommends dolutegravir (DTG), an HIV integrase inhibitor, as a key component of first-line antiretroviral therapy (ART). In Brazil, DTG has been used since 2017 as the preferred initial treatment for people living with HIV (PLWH), combined with lamivudine (3TC) and tenofovir (TDF). Objective: To analyze the incidence and associated factors of viral resistance mutations to integrase among PLWH initiating ART with a DTG-containing regimen and who underwent genotypic testing after treatment initiation. Methods: This is a retrospective cohort study including individuals initiating ART in Brazil, identified through probabilistic matching across three Ministry of Health databases: the Sistema de Controle Logístico de Medicamentos (Siclom), Sistema de Controle de Exames Laboratoriais (Siscel) and Sistema de Controle de Exames de Genotipagem (Sisgeno). Sociodemographic, clinical, and treatment-related characteristics were analyzed for individuals with recorded genotyping from January 2017 to December 2019. Resistance levels to DTG were classified according to the Stanford HIV Drug Resistance Database. Adherence was measured by the proportion of days covered (PDC) using the CMA5 calculation, with optimal adherence defined as PDC ≥ 80%. Factors associated with DTG resistance were evaluated using Cox regression. Results: Of the 430 participants, 30 (7.0%) exhibited resistance to DTG, with four individuals showing high-level resistance mutations. The most frequent major mutations were N155H, found in nine individuals, followed by E138KAE (n=7), G140SDGAE and Q148HR (n=6), R263K (n=5), and E92QVG (n=4), S147G, and T66K (n=1). The most common minor mutations included L101I (n=17) and A124T (n=14). In multivariate analysis, risk factors associated with DTG resistance included male sex (HR: 4.7; 95% CI: 1.89 – 11.7), previous use of raltegravir after requiring a treatment switch (HR: 3.26; 1.54 – 6.94), suboptimal adherence < 80% (HR: 3.3; 1.31 – 8.35), and resistance to the NRTI class (HR: 3.17; 95% CI: 1.44 – 6.9). Conclusion: The observed proportion of mutations highlights the presence of DTG resistance among treatment-naive individuals. Ongoing DTG resistance surveillance should focus on individual, clinical, and treatment-related characteristics.