Phylogenetic investigation of HCV-4d epidemic in Paris MSM HIV population reveals a still active outbreak and a strong link to the Netherlands

Abstract

Objectives: The hepatitis C virus (HCV) epidemic is evolving quickly despite new treatments, and due to behaviour changes increasing at-risk situations. We investigated potential origins and evolution of the HCV-4d French emergence among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM), in Paris in 2003. Methods: We analysed all HCV sequences from the initial Paris outbreak with all newly available sequences publicly available, including sampling date and geographical location, resulting in 184, 68, 156, 107, 13 and 2 sequences from France, The Netherlands, other European countries, Africa, the Middle East or Turkey, Americas and Asia, respectively. Phylogenetic reconstruction was performed using maximum likelihood and Bayesian approaches. Results: HCV-4d sequences from Europe were strongly separated from non-European sequences. Sequences from the initial Paris outbreak were all included into two well-separated and supported clusters with branch support at 100%, mean genetic distance <2.8 substitutions/100 nucleotides and >3.4 substitutions/100 nucleotides between their common ancestor and the previous node. The largest cluster interleaved French (n ¼ 98) and Dutch (n ¼ 28) sequences, suggesting several translocations between these countries. This cluster included 41 French sequences from Lyon sampled after 2014, highlighting its continuous spread within France since the initial outbreak. The smallest cluster included one Paris sequence with UK sequences (n ¼ 9). Discussion: A few previous works have shown HCV-4d transmissions occurring between a few countries. In our work, we suggest a new and large connection between France and The Netherlands MSM communities and highlight a well-separated pan-European transmission network. Large collaborative networks are needed to investigate ongoing transmissions across countries and help specific prevention measures.

Hepatitis C virus (HCV) incidence among men who have sex with men (MSM) living with HIV: results from the French Hospital Database on HIV (ANRS CO4-FHDH) cohort study, 2014 to 2017

“…For example, in the Netherlands, DAAs became widely available in 2015, and two prospective studies among MSM living with HIV in 2014 and 2016 reported a 51% decrease in HCV incidence between 2014 and 2016 [ 21 ]. Interestingly, a study published in 2020 analysing phylogenetic HCV strains among HIV-infected MSM diagnosed with HCV subtype 4d during the 2003–2007 HCV outbreak highlighted the close links between the French and the Dutch MSM communities [ 22 ]. Additionally, a decreasing trend was observed among MSM living with HIV in the United Kingdom between 2013 and 2018 [ 23 ].…”

Incidence of recently acquired hepatitis C virus infection among HIV‐infected patients in southern Spain

“…In the last decade, numerous outbreaks of recently acquired hepatitis C virus infection (RAHC) have been described among people living with HIV (PLWH) worldwide, mainly in HIV‐positive men who have sex with men (MSM) [1–9]. The increased incidence of RAHC in HIV‐positive MSM has been attributed to several factors such as a higher hepatitis C virus (HCV) load in blood and semen [10], sexual practices with an increased risk of mucosal damage, the presence of ulcerative sexually transmitted diseases, a larger number of sexual partners and the use of chem‐sex [11].…”

The Emergence of Hepatitis C Virus Genotype 4d Among Human Immunodeficiency Virus–Infected Patients in Mexico City: A Molecular Epidemiological Study

“…25 However, the phylogenetic results of the NS5B region suggested a likely (although inconclusive) association with a France origin, where the genotype 4d has been endemic in the MSM population since about 2000. 2 There are data of extensive dissemination from this origin to neighbor countries 9 and transcontinental. 6 Sexual transmission of HCV in the MSM population with and without HIV infection, even heterosexual transmission as reported in the female HIV-infected patient in this study, is a public health problem nowadays despite the extensive use of DAA.…”