Factors associated with phylogenetic clustering of hepatitis C virus, mainly among people who inject drugs who access HIV prevention services in South Africa, 2016–2017

People who inject drugs (PWID) are disproportionately burdened with hepatitis C virus (HCV) infection in South Africa (SA). Transmission dynamics can be inferred using phylogenetic clustering to inform prevention interventions. We utilized Core-E2 sequences and demographic data to investigate factors associated with HCV phylogenetic clustering among PWID and men who have sex with men (MSM) who inject drugs in SA. Previously genotyped samples (n = 285) that met the selection criteria were extracted, amplified, and Sanger sequenced. Phylogenetic trees were inferred using maximum likelihood implemented in RAxML (Cipres Gateway). Transmission clusters were determined in Clusterpicker using a 90% bootstrap threshold and a genetic distance cut-off on genetic similarity of ≤3.5%. Factors associated with clustering were assessed using logistic regression. Phylogenetic clustering of Core-E2 sequences was observed for 55% (78 of 141) of participant samples that were successfully sequenced, including 50 (64.1%) with genotype 1a and 28 (35.9%) with genotype 3a. Twelve clusters were identified, including six clusters each for genotypes 1a and 3a. Among genotype 1a, the cluster size ranged from 3 to 15 participants. Among genotype 3a, the cluster size ranged from 3 to 9 participants. Clustering among the mixed ancestry group in Cape Town was noted for ages 18-55. Factors independently associated with phylogenetic clustering included sharing a needle (adjusted odds ratio [aOR] 4.02, 95% confidence interval [CI] 1.08-14.87, p = 0.037), age ≥ 29 years (aOR 3.00, 95% CI 1.22-7.37, p = 0.016), and mixed ancestry race (aOR 6.11, 95% CI 1.87-19.95, p = 0.003). These data highlight the urgent need to reduce transmission by providing sufficient sterile needles and syringes and tailored education to prevent HCV transmission among older, experienced PWID.