Expanding epidemic of recently acquired HCV in HIV-coinfected patients over a period of 10 years

Abstract

Background & aims: Ongoing transmission of HCV infections is associated with risk factors such as drug injection, needlestick injuries, and men who have sex with men (MSM). Ways of transmission, the course of acute infection, changes of virologic features, and incidence over time are not well known.

Methods: Over a period of 10 years, n = 161 patients with recently acquired HCV infection (RAHC) (median follow-up 6.8 years) were prospectively enrolled. NS5B sequencing was performed to re-evaluate the HCV genotype (GT) and for phylogenetic analyses.

Results: Patients with RAHC were mainly male (92.5%), MSM (90.1%), and HIV-coinfected (86.3%). Transmission risk factors for MSM and non-MSM were sexual risk behaviour (100 and 6.3%, respectively), injection drug use (9.7 and 37.5%, respectively), and nasal drug use (15.2 and 0%, respectively). Spontaneous and interferon- or direct-acting antiviral-based clearance rates were 13.6, 84.3 and 93.4%, respectively. Mean RAHC declined from 19.8 in the first to 13.2 in the past five study years. Although the majority of infections was caused by HCV GT1a, the frequency of HCV GT4d and slightly HCV GT3a increased over time. No relevant clustering of HCV isolates was observed in non-MSM. However, 45% of HCV GT1a and 100% of HCV GT4d MSM cases clustered with MSM isolates from other countries. Travel-associated infections were supported by personal data in an MSM subgroup. No international clustering was detected in MSM with HCV GT1b or HCV GT3a.

Conclusions: RAHCs were mainly diagnosed in HIV-coinfected MSM patients and were associated with sexual risk behaviour. Spontaneous clearance rates were low, and phylogenetic clusters were observed in the majority of patients.

Impact and implications: We evaluated the occurrence and transmission of recently acquired HCV infections (RAHCs) over a period of 10 years. Our data demonstrate that the presence of RAHC was mainly found in HIV-coinfected MSM, with internationally connected transmission networks being observed in the majority of patients. Spontaneous clearance rates were low, and reinfection rates increased mainly driven by a small subset of MSM patients with high-risk behaviour.

Keywords: Acute HCV infection; HCV; HIV coinfection; MSM; NS5B phylogeny.

Graphical abstract

Fig. 1

Characteristics of HCV-monoinfected and HCV/HIV-coinfected patients with recently acquired hepatitis C infection. (A) Annual recently acquired hepatitis C cases and (B) prevalence of different HCV genotypes and subtypes over the study time period. GT, genotype.

Fig. 2

Differentiation of viral relapse vs. HCV reinfection by phylogenetic trees in acute hepatitis C infections with (A) HCV genotype 1a and (B) HCV genotype 4d. Baseline and posttreatment sequences are marked by a circle and triangle each in the same colour, respectively. Control samples are shown in white and marked as BL and REL. aHCV, acute HCV; BL, baseline; Cont., control; REL, relapse.

Fig. 3

Phylogenetic trees based on HCV NS5B sequencing analyses conducted at the time point of acute hepatitis C diagnosis in patients with (A) HCV genotype 1a, (B) HCV genotype 1b, (C) HCV genotype 3a, and (D) HCV genotype 4d. Clusters are illustrated by triangles, and numbers in the triangles represent the number of sequences in each cluster. Country of origin is shaded as follows: () non-MSM, Frankfurt, Germany; () MSM, Frankfurt, Germany; (red) MSM (published sequences), Germany; (dark blue) MSM (published sequences), UK; (orange) MSM (published sequences), Netherlands; (grey) MSM (published sequences), Switzerland; (yellow) MSM (published sequences), Spain; (light blue) MSM (published sequences), USA; (pink) MSM (published sequences), Canada; (purple) MSM (published sequences), Australia; (green) MSM (published sequences), France. GT, genotype.

Fig. 3

Phylogenetic trees based on HCV NS5B sequencing analyses conducted at the time point of acute hepatitis C diagnosis in patients with (A) HCV genotype 1a, (B) HCV genotype 1b, (C) HCV genotype 3a, and (D) HCV genotype 4d. Clusters are illustrated by triangles, and numbers in the triangles represent the number of sequences in each cluster. Country of origin is shaded as follows: () non-MSM, Frankfurt, Germany; () MSM, Frankfurt, Germany; (red) MSM (published sequences), Germany; (dark blue) MSM (published sequences), UK; (orange) MSM (published sequences), Netherlands; (grey) MSM (published sequences), Switzerland; (yellow) MSM (published sequences), Spain; (light blue) MSM (published sequences), USA; (pink) MSM (published sequences), Canada; (purple) MSM (published sequences), Australia; (green) MSM (published sequences), France. GT, genotype.