Earlier Initiation of Antiretroviral Treatment Coincides With an Initial Control of the HIV-1 Sub-Subtype F1 Outbreak Among Men-Having-Sex-With-Men in Flanders, Belgium.

Lore Vinken,Sigi Van Den Wijngaert,Katrien Fransen,Anders Sönnerborg,Marc Van Ranst,Philippe Lemey,Laurent Debaisieux,Francesca Incardona,Carole Seguin-Devaux,Lize Cuypers,Martine Peeters,Rolf Kaiser,Simona Paraschiv,Ivailo Alexiev,Chris Verhofstede,Anne-Mieke Vandamme,Murat Sayan,Claudia Balotta,Tanja Stadler,Kristel Van Laethem,Roger Paredes,Ellen Vancutsem,Jean-Louis Ruelle ,Sergio Garcı́a Ribas ,Perpétua Gómes

doi:10.3389/fmicb.2019.00613

Abstract

Human immunodeficiency virus type 1 (HIV-1) non-B subtype infections occurred in Belgium since the 1980s, mainly amongst migrants and heterosexuals, whereas subtype B predominated in men-having-sex-with-men (MSM). In the last decade, the diagnosis of F1 sub-subtype in particular has increased substantially, which prompted us to perform a detailed reconstruction of its epidemiological history. To this purpose, the Belgian AIDS Reference Laboratories collected HIV-1 pol sequences from all sub-subtype F1-infected patients for whom genotypic drug resistance testing was requested as part of routine clinical follow-up. This data was complemented with HIV-1 pol sequences from countries with a high burden of F1 infections or a potential role in the global origin of sub-subtype F1. The molecular epidemiology of the Belgian subtype F1 epidemic was investigated using Bayesian phylogenetic inference and transmission dynamics were characterized based on birth-death models. F1 sequences were retained from 297 patients diagnosed and linked to care in Belgium between 1988 and 2015. Phylogenetic inference indicated that among the 297 Belgian F1 sequences, 191 belonged to a monophyletic group that mainly contained sequences from people likely infected in Belgium (OR 26.67, 95% CI 9.59–74.15), diagnosed in Flanders (OR 7.28, 95% CI 4.23–12.53), diagnosed at a recent stage of infection (OR 7.19, 95% CI 2.88-17.95) or declared to be MSM (OR 34.8, 95% CI 16.0–75.6). Together with a Spanish clade, this Belgian clade was embedded in the genetic diversity of Brazilian subtype F1 strains and most probably emerged after one or only a few migration events from Brazil to the European continent before 2002. The origin of the Belgian outbreak was dated back to 2002 (95% higher posterior density 2000–2004) and birth-death models suggested that its extensive growth had been controlled (Re < 1) by 2012, coinciding with a time period where delay in antiretroviral treatment initiation substantially declined. In conclusion, phylogenetic reconstruction of the Belgian HIV-1 sub-subtype F1 epidemic illustrates the introduction and substantial dissemination of viral strains in a geographically restricted risk group that was most likely controlled by effective treatment as prevention.

Highlights

Human immunodeficiency virus type 1 (HIV-1) originated after at least four separate cross-species transmission events from nonhuman primates to humans in central Africa, which resulted in four groups (M, N, O, and P) that emerged in the early twentieth century (Peeters et al, 2014)
The HIV-1 subtype B lineage that is responsible for the majority of HIV-1 infections in Europe, was first exported from central Africa to the Caribbean region around 1967 from where it was subsequently introduced in the United States and spread over to other American and European countries, mainly via networks of men-having-sex-with-men (MSM) and people who injects drugs (PWID) (Abecasis et al, 2013; Junqueira and Almeida, 2016; Magiorkinis et al, 2016; Worobey et al, 2016)
Up to February 2015, 297 HIV-1 sub-subtype F1 infections were newly diagnosed in the participating Belgian AIDS reference laboratories (ARL) (Figure 1), of which 137 were analyzed in Antwerp (46%), 95 in Brussels (32%), 38 in Leuven (13%), and 27 in Ghent (9%)

Summary

Introduction

Human immunodeficiency virus type 1 (HIV-1) originated after at least four separate cross-species transmission events from nonhuman primates to humans in central Africa, which resulted in four groups (M, N, O, and P) that emerged in the early twentieth century (Peeters et al, 2014). Belgian MSM remained almost exclusively infected with subtype B strains These findings were confirmed in an independent study where heterosexual contact, African origin and more recent diagnosis were predictors for non-B infection in HIV-1 patients diagnosed between 1983 and 2001 in two other Belgian cities (Brussels and Leuven) (Snoeck et al, 2004). HIV-1 non-B infections in Belgium, of which HIV-1 subtype A, C, and CRF02_AG infections were the most prevalent, were associated to migrants from sub-Saharan Africa and individuals showing heterosexual risk behavior (Vercauteren et al, 2008; Chalmet et al, 2010; Pineda-Peña et al, 2014)

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