Nationwide study of drug resistance mutations in hiv-1 infected individuals under antiretroviral therapy in Brazil

Ana Santos-Pereira, Vera Triunfante, Pedro M.M. Araújo, Joana Martins, Helena Soares, Eva Poveda, Bernardino Souto, Nuno S. Osório

Research output: Contribution to journalArticlepeer-review

Abstract

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008– 2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse tran-scriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

Original languageEnglish
Article number5304
JournalInternational Journal of Molecular Sciences
Volume22
Issue number10
DOIs
Publication statusPublished - 2 May 2021

Keywords

  • Antiretroviral treatment failure
  • Brazilian cohort study
  • Drug resistance mutations
  • HIV-1
  • K65R
  • Tenofovir

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