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

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 ( R e < 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.

Dynamics of HIV-1 Molecular Networks Reveal Effective Control of Large Transmission Clusters in an Area Affected by an Epidemic of Multiple HIV Subtypes

“…For example, in our study a large number of new cases were referred from other surveillance sites to the study center for treatment since 2014; therefore, a peak was observed in the cluster growth predictor curve of many clusters in 2014 (orange lines in Figure 4), whereas no corresponding change was observed in the PDR curves (blue lines in Figure 4). R e , the third phylodynamic parameter that is based on sequence diversity, reflects the efficiency with which an infectious agent is transmitted and is frequently used to model infection dynamics (Novitsky et al, 2015;Ragonnet-Cronin et al, 2018;Jovanovic et al, 2019;Lorenzin et al, 2019;Vasylyeva et al, 2019;Vinken et al, 2019;Zai et al, 2020). We found that R e was accurate and reliable.…”

“…R e of each large cluster (≥ 10 cases) was estimated with the birth-death skyline serial model in BEAST v2.4.2 (Jovanovic et al, 2019;Vasylyeva et al, 2019;Vinken et al, 2019;Dennis et al, 2020). R e represents the average number of secondary infections caused by a typical infected individual when only part of the population is susceptible.…”

“…According to our data, early ART (initiated within 6 months after diagnosis) increased from 24 to 79% between 2008 and 2016 ( Figure 5), which coincided with decreases in both the ongoing transmission of large clusters and the number of newly diagnosed RHI cases in large clusters, indicating the control of HIV transmission and the effectiveness of preventative treatments (Figures 4, 5). Similarly, a study from Belgium demonstrated that the expansion of an outbreak cluster (subtype F1 outbreak among MSM) was controlled by 2012 (R e < 1), coinciding with a decrease in rates of delayed ART initiation as a result of implementation of the immediate ART initiation policy (Vinken et al, 2019).…”

Identification of CRF89_BF, a new member of an HIV-1 circulating BF intersubtype recombinant form family widely spread in South America

“…The identi cation of CRF89_BF infections in Spain and other European countries, mainly in South American immigrants, re ects the increasing relation between the South American and European HIV-1 epidemics, which is also re ected in the expansion in Western Europe of clusters of South American strains of subtypes C [53][54][55][56] and F1 [31,[57][58][59], of CRF12_BF [60] and of CRF17_BF [54], and in the identi cation in Western Europe of CRFs derived from parental strains of South American ancestry [61][62][63].…”

Phylogenetics applied to the human immunodeficiency virus type 1 (HIV-1): from the cross-species transmissions to the contact network inferences

“…A recent study dated back the origin of a Belgian HIV-1 subtype F1 epidemic among men having sex with men (MSM) to the early 2000s and suggested that its extensive growth was controlled about 10 years later, most likely due to highly active antiretroviral therapy (ART) as prevention. (17) Another study estimated that major shifts in HIV-1 transmission for subtypes B and G Portuguese clades occurred around the late 1990s and early 2000s, also coinciding with the introduction of ART and the scale-up of harm reduction for IDU. (18) Analyses of the HIV-1 subtype C epidemic in heterosexual population from southern Brazil support that major changes in viral transmission dynamics (transient epidemic stabilisation and resume epidemic increase) coincides with people's behavioral changes driven by implementation of prevention efforts and perception of risk for HIV transmission.…”