Comprehensive Characterization of HIV-1 Molecular Epidemiology and Demographic History in the Brazilian Region Most Heavily Affected by AIDS

Abstract

The high incidence of AIDS cases and the dominance of HIV-1 subtype C infections are two features that distinguish the HIV-1 epidemic in the two southernmost Brazilian states (Rio Grande do Sul [RS] and Santa Catarina [SC]) from the epidemic in other parts of the country. Nevertheless, previous studies on HIV molecular epidemiology were conducted mainly in capital cities, and a more comprehensive understanding of factors driving this unique epidemic in Brazil is necessary. Blood samples were collected from individuals in 13 municipalities in the Brazilian southern region. HIV-1 env and pol genes were submitted to phylogenetic analyses for assignment of subtype, and viral population phylodynamics were reconstructed by applying Skygrid and logistic coalescent models in a Bayesian analysis. A high prevalence of subtype C was observed in all sampled locations; however, an increased frequency of recombinant strains was found in RS, with evidence for new circulating forms (CRFs). In the SC state, subtype B and C epidemics were associated with distinct exposure groups. Although logistic models estimated similar growth rates for HIV-1 subtype C (HIV-1C) and HIV-1B, a Skygrid plot reveals that the former epidemic has been expanding for a longer time. Our results highlight a consistent expansion of HIV-1C in south Brazil, and we also discuss how heterosexual and men who have sex with men (MSM) transmission chains might have impacted the current prevalence of HIV-1 subtypes in this region. IMPORTANCEThe AIDS epidemic in south Brazil is expanding rapidly, but the circumstances driving this condition are not well known. A high prevalence of HIV-1 subtype C was reported in the capital cities of this region, in contrast to the subtype B dominance in the rest of the country. This study sought to comparatively investigate the HIV-1 subtype B and C epidemics by sampling individuals from several cities in the two states with the highest AIDS incidences in Brazil. Our analyses showed distinct epidemic growth curves for the two epidemics, and we also found evidence suggesting that separate transmission chains may be impacting the viral phylodynamics and the emergence of new recombinant forms. High-level molecular diversity is one of the main features of HIV-1. Due to the very high replication rate and the lack of a proofreading activity of the viral reverse transcriptase (RT) enzyme, HIV-1 group M, the pandemic strain, has evolved into a diverse number of variants (1). Among 9 HIV-1 group M subtypes, HIV-1 subtype C (HIV-1C) is responsible for Ͼ50% of infections worldwide, occurring mostly in southern and east African countries and India. HIV-1B, in turn, is widely dispersed throughout the world, being the dominant strain in Europe and in the Americas, but with a worldwide prevalence of only 10% (1, 2). The high level of variability of HIV-1 is also a consequence of the genetic recombination process, which can occur in unique recombinant forms (URFs), when fewer than three individuals are infected, or in circulating forms (C...

Inferring population dynamics of HIV-1 subtype C epidemics in Eastern Africa and Southern Brazil applying different Bayesian phylodynamics approaches

“…Notably, the epidemic growth rate inferred for the Brazilian C EA sub-epidemic was very similar to those obtained for the African C EA sub-epidemics despite significantly distinctive history of human conflicts in those regions. The exponential growth phase of the C EA/BR sub-epidemic matches with a period in which public health system was unaware about the severity of the epidemic 53 and the C EA/BR subclade was efficiently disseminated in Southern Brazil through heterosexual (HET) networks 2 , 13 , 54 , similar to that observed in Eastern Africa. This suggests that the absence of prevention efforts and the predominant viral transmission through HET route may have been the common driving forces of the early dynamics of the C EA sub-epidemics in Eastern African and Southern Brazil.…”

“…A recent study using BSKG to analyze the population dynamics of the C EA/BR sub-epidemic from pol and env sequences from HET and men having sex with men (MSM) individuals reported a continuous increase in the Ne until mid to late 2000’s that was associated with the recent expansion of subtype C throughout the MSM group 13 . Interestingly, universal access to free fully suppressive ARV therapy is available in Brazil since the late 1990s 61 , 62 and an association between ARV treatment availability and increases in sexual risk behavior (and consequent rise in HIV incidence) have been previously reported among MSM from developed countries 68 – 71 .…”

“…The evolutionary analyses of the C EA sub-epidemics performed so far mostly address questions about the place and timing of outbreaks onset, focusing on the reconstruction of the geographic dissemination pathways of this viral clade 2 , 5 , 6 , 8 – 12 . Studies on the population dynamics of C EA sub-epidemics, while key to understand their historical epidemic growth trends, epidemic potential and ecological processes shaping their evolution, have been much less frequent 13 , 14 .…”

Identification of New HIV-1 Circulating Recombinant Forms CRF81_cpx and CRF99_BF1 in Central Western Brazil and of Unique BF1 Recombinant Forms

“…The cocirculation of distinct HIV-1 subtypes is known to increase the chances of coinfection and of the generation of BF1, F1CB, BC, and CF1 intersubtype recombinant viruses (Jetzt et al, 2000; Faria et al, 2014). In the last decade, different circulating recombinant forms (CRFs) and unique recombinant forms (URFs) have been described including BC recombinants especially in the Southern and BF1 recombinants in different Brazilian regions (Guimarães et al, 2008, 2010; Passaes et al, 2009; Ferreira et al, 2011; da Silveira et al, 2012; Pessôa et al, 2014b, 2016; Moura et al, 2015a,b; Gräf et al, 2016; Lima et al, 2016b; Reis et al, 2017).…”

Molecular Epidemiology of the HIV Epidemic in Three German Metropolitan Regions – Cologne/Bonn, Munich and Hannover, 1999–2016

“…The overall number of HIV infected patients is estimated at 84,700 (78,300–91,100) in Germany 4 . Similar to the epidemic across Europe, men-who-have-sex-with-men (MSM) bear the major burden of new infections 1 , 2 , 5 , 6 . Increasing HIV incidence in MSM can be attributable to an increase of risky sex in particular in young MSM, often associated with a simultaneous intake of recreational drugs such as methamphetamine, mephedrone, poppers, or cocaine 7 .…”