Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil.

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

doi:10.3390/ijms22105304

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 transcriptase 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.

Highlights

According to the Joint United Nations Programme on HIV/acquired immunodeficiency syndrome (AIDS) (UNAIDS), 690,000 individuals died in 2019 of human immunodeficiency virus (HIV) infection-related causes. the global number of new infections (1.7 million) has been reduced by 23%, since 2010, Latin America has presented a 21% increase
Prevalence across the 27 Brazilian federative units focusing on 20,226 HIV-1 infected patients under different Antiretroviral therapy (ART) schemes, with viral sequence genotyped between 2008 and
A high prevalence of surveillance drug-resistance mutations (SDRM) was observed with 84.1% of the infected individuals presenting at least one drug resistance mutation

Summary

Introduction

According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), 690,000 individuals died in 2019 of human immunodeficiency virus (HIV) infection-related causes. the global number of new infections (1.7 million) has been reduced by 23%, since 2010, Latin America has presented a 21% increase. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), 690,000 individuals died in 2019 of human immunodeficiency virus (HIV) infection-related causes. Brazil experienced an increase of 17%, with 48,000 new reported infections and 14,000 acquired immunodeficiency syndrome (AIDS)-related deaths, in the same year [1]. Antiretroviral therapy (ART) significantly improves patients’ survival, increasing life expectancy and quality [2,3,4]. It plays a relevant role in the prevention of HIV-1 transmission in the population [5,6,7,8]. The emergence of drug resistance mutations (DRM) represents a major threat for the continued control of HIV replication, and consequent potential increase in the transmission of viral strains with DRM [9,10]

Methods

Results

Conclusion