Estimating HIV-1 Genetic Diversity in Brazil Through Next-Generation Sequencing.

Brunna M Alves,Patrícia Recordon-Pinson,Marcelo A Soares,Vanusa P Da Hora,Juliana D Siqueira,Sabri Sanabani,Hervé Fleury,Isabel M Prellwitz,Esmeralda A Soares,Ornella M Botelho

doi:10.3389/fmicb.2019.00749

Abstract

Approximately 36.7 million people were living with the human immunodeficiency virus (HIV) at the end of 2016 according to UNAIDS, representing a global prevalence rate of 0.8%. In Brazil, an HIV prevalence of 0.24% has been estimated, which represents approximately 830,000 individuals living with the virus. As a touristic and commercial hub in Latin America, Brazil harbors an elevated HIV genetic variability, further contributed by the selective pressure exerted by the host immune system and by antiretroviral treatment. Through the progress of the next-generation sequencing (NGS) techniques, it has been possible to expand the study of HIV genetic diversity, evolutionary, and epidemic processes, allowing the generation of HIV complete or near full-length genomes (NFLG) and improving the characterization of intra- and interhost diversity of viral populations. Greater sensitivity in the detection of viral recombinant forms represents one of the major improvements associated with this development. It is possible to identify unique or circulating recombinant forms using the near full-length viral genomes with increasing accuracy. It also permits the characterization of multiple viral infections within individual hosts. Previous Brazilian studies using NGS to analyze HIV diversity were able to identify several distinct unique and circulating recombinant forms and evidenced dual infections. These data unveiled unprecedented high rates of viral recombination and highlighted that novel recombinants are continually arising in the Brazilian epidemic. In the pooled analysis depicted in this report, HIV subtypes have been determined from HIV-positive patients in five states of Brazil with some of the highest HIV prevalence, three in the Southeast (Rio de Janeiro, São Paulo, and Minas Gerais), one in the Northeast (Pernambuco) and one in the South (Rio Grande do Sul). Combined data analysis showed a significant prevalence of recombinant forms (29%; 101/350), and a similar 26% when only NFLGs were considered. Moreover, the analysis was able to evidence the occurrence of multiple infections in some individuals. Our data highlight the great HIV genetic diversity found in Brazil and unveils a more accurate scenario of the HIV evolutionary dynamics in the region.

Highlights

The first registry of AIDS was reported in the beginning of the 1980s, and until now 77 million people have become infected with human immunodeficiency virus (HIV) and 35 million have died from AIDS-related causes
These were from HIV-1-seropositive patients recruited between February 2016 and December 2017 during the routine services conducted at Sexually Transmitted Diseases/HIV ambulatory at Hospital Federal de Ipanema (HFI) and at Hospital Universitário Clementino Fraga Filho (HU-UFRJ), both located in Rio de Janeiro, southeastern Brazil, and at Hospital Universitário Dr Miguel Riet Corrêa Jr. (HU-FURG), located in Rio Grande, southern Brazil
We included data previously published by our group from patients followed-up at HFI and all HIV-1 sequences obtained by next-generation sequencing (NGS) publicly available

Summary

Introduction

The first registry of AIDS was reported in the beginning of the 1980s, and until now 77 million people have become infected with human immunodeficiency virus (HIV) and 35 million have died from AIDS-related causes. Harboring over one-third of the total population of Latin America, Brazil accounts for nearly half of the new HIV infections and of the estimated total of individuals living with HIV/AIDS (48 and 46%, respectively) in the region (UNAIDS, 2018). This scenario, along with the high errorprone rate of the viral reverse transcriptase (RT), high virus replication rates and recombination events, contributes to the remarkable accumulation of genetic diversity in its population during the course of infection, further influenced by selective pressure exerted by the host immune system and by antiretroviral treatment (Roberts et al, 1988; Overbaugh and Bangham, 2001; Zhuang et al, 2002; Santoro and Perno, 2013). Southern Brazil, presents a distinct epidemiological pattern, with a higher prevalence of subtypes C, B, and BC recombinants (Cardoso et al, 2009; Machado et al, 2009, 2017; de Medeiros et al, 2011; Almeida et al, 2012; Graf and Pinto, 2013; Velasco-de-Castro et al, 2014; Junqueira and Almeida, 2016; Pessoa et al, 2016; Delatorre et al, 2017; Filho and Brites, 2017; Lima et al, 2017)

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Conclusion