Patterns and correlates of hepatitis C virus phylogenetic clustering among people living with HIV in Australia in the direct-acting antiviral era: A molecular epidemiology study among participants in the CEASE cohort

Sofia R Bartlett; Andrey Verich; Joanne Carson; Samira Hosseini-Hooshyar; Phillip Read; David Baker; Jeffrey J Post; Robert Finlayson; Mark Bloch; Joseph S Doyle; David Shaw; Margaret Hellard; Maria Martinez; Philippa Marks; Gregory J Dore; Gail V Matthews; Tanya Applegate; Marianne Martinello

doi:10.1002/hsr2.719

Patterns and correlates of hepatitis C virus phylogenetic clustering among people living with HIV in Australia in the direct-acting antiviral era: A molecular epidemiology study among participants in the CEASE cohort

Health Sci Rep. 2022 Aug 18;5(5):e719. doi: 10.1002/hsr2.719. eCollection 2022 Sep.

Authors

Sofia R Bartlett^{1

2}, Andrey Verich³, Joanne Carson³, Samira Hosseini-Hooshyar³, Phillip Read⁴, David Baker⁵, Jeffrey J Post^{6

7

8}, Robert Finlayson⁹, Mark Bloch¹⁰, Joseph S Doyle^{11

12}, David Shaw¹³, Margaret Hellard^{11

12}, Maria Martinez³, Philippa Marks³, Gregory J Dore^{3

14}, Gail V Matthews^{3

14}, Tanya Applegate³, Marianne Martinello³

Affiliations

¹ British Columbia Centre for Disease Control Vancouver British Columbia Canada.
² School of Population and Public Health University of British Columbia Vancouver British Columbia Canada.
³ The Kirby Institute, UNSW Sydney Sydney New South Wales Australia.
⁴ Kirketon Road Centre Sydney New South Wales Australia.
⁵ East Sydney Doctors Sydney New South Wales Australia.
⁶ The Albion Centre Sydney New South Wales Australia.
⁷ Department of Infectious Diseases Prince of Wales Hospital Sydney New South Wales Australia.
⁸ Prince of Wales Clinical School University of New South Wales Sydney Sydney New South Wales Australia.
⁹ Taylor Square Private Clinic Sydney New South Wales Australia.
¹⁰ Holdsworth House Medical Practice Sydney New South Wales Australia.
¹¹ Department of Infectious Diseases Alfred Health & Monash University Melbourne Victoria Australia.
¹² Burnet Institute, Melbourne Victoria Australia.
¹³ Royal Adelaide Hospital Adelaide South Australia Australia.
¹⁴ St Vincent's Hospital Sydney New South Wales Australia.

Abstract

Background and aims: In moving towards the elimination of hepatitis C virus (HCV) infection among people living with HIV, understanding HCV transmission patterns may provide insights to guide and evaluate interventions. In this study, we evaluated patterns of, and factors associated with HCV phylogenetic clustering among people living with HIV/HCV co-infection in Australia in the direct-acting antiviral era.

Methods: HCV RNA was extracted from dried blood spot (DBS) samples collected between 2014 and 2018 in the CEASE cohort study. The HCV Core-E2 region was amplified by a polymerase chain reaction and Sanger sequenced. Maximum likelihood phylogenetic trees (1000 bootstrap replicates) were used to identify patterns of clustering (3% genetic distance threshold). Mixed-effects logistic regression was used to determine correlates of phylogenetic clustering. Factors assessed were sexual risk behavior, education, injecting drug use, housing, employment, HIV viral load, age, sex, and sexuality.

Results: Phylogenetic trees were reconstructed for HCV subtype 1a (n = 139) and 3a (n = 63) sequences, with 29% (58/202) in a pair or cluster. Overall (n = 202), phylogenetic clustering was positively associated with younger age (under 40; adjusted odds ratio [aOR] 2.52, 95% confidence interval [CI] 1.20-5.29), and among gay and bisexual men (n = 168), was positively associated with younger age (aOR 2.61, 95% CI 1.10-6.19), higher education (aOR 2.58, 95% CI 1.09-6.13), and reporting high-risk sexual behavior (aOR 3.94, 95% CI 1.31-11.84). During follow-up, five reinfections were observed, but none were in phylogenetic clusters.

Conclusion: This study found a high proportion of phylogenetic relatedness, predominantly among younger people and gay and bisexual men reporting high-risk sexual behavior. Despite this, few reinfections were observed, and reinfections demonstrated little relationship with known clusters. These findings highlight the importance of rapid HCV treatment initiation, together with monitoring of the phylogeny.

Keywords: HIV; gay and bisexual men (GBM); hepatitis C; molecular sequencing; phylogenetic analysis.