IN-DEPTH CHARACTERIZATION OF HIV RESISTANCE TO INTEGRASE INHIBITORS IN BRAZIL
. Veras N. Mar 4, 2019; 258758
Topic: Other
Dr. Nazle Veras
Dr. Nazle Veras
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Abstract
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Due to increasing HIV drug resistance, Brazil was one of the first countries to adopt Dolutegravir (DTG) in first-line antiretroviral therapy (ART). The Ministry of Health of Brazil offers genotyping tests to all individuals under an integrase inhibitor (INI) based regimen experiencing virological failure. Using real life data, we aimed to characterize HIV genotypic resistance to Raltegravir (RAL) and DTG in Brazil in order to better understand factors related to the development of INI resistance-associated mutations (RAM), and to depict INI RAM transmission chains.

HIV integrase sequences from 2012-2018 were selected from the National System for Genotyping Control. The presence of INI RAM (Stanford HIVdb Program) and HIV subtype (Rega HIV Subtyping tool) were characterized. Socio-demographic, clinical (CD4 count and viral load/VL), and ART history data were assessed. A Pearson Chi-square test was carried out. INI RAM transmission clades were characterized by Bayesian phylogenetics.

We analyzed 1,467 HIV integrase sequences from RAL- and/or DTG-experienced individuals. HIV resistant strains were identified in 21.7% for RAL and 0.7% for DTG. In 2017, following the use of DTG in first-line ART, individuals on RAL-based regimen switched to DTG. As a reflection of DTG’s higher genetic barrier, resistance to INI has have been slightly decreasing to 13.7% and 0.3% in 2018 for RAL and DTG, respectively. Indeed, we did not identify any DTG resistant lineages in samples from individuals under DTG first-line ART. The prevalence of RAL and DTG resistant strains was similar, regardless of demographic and clinical data, including regional sustained VL levels. INI RAMs at positions G140 (7.0%) and E138 (1.0%) were most prevalent. Overall, subtype B (69.9%) was the most prevalent, followed by C (13.7%), F (8.9%) and recombinant forms (6.7%). Sequences presenting INI RAM were dispersed in phylogenetic trees for subtypes B and C, showing no specific INI RAM transmission clade, considering both the national level and the five Brazilian geographic regions, separately.

INI RAM monitoring revealed a short-term decrease in resistance to INI, even after DTG large-scale use. In addition, phylogenetics revealed that INI RAM does not occur in a particular population group or geographic region. Hence, the successful pioneering implementation of DTG goes beyond costs savings but healthcare efficacy, corroborating to sustaintability of DTG as first-line ART in a public health program.
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