Predictors of Transmission Risk in Hepatitis C

Investigators found that young age, high HCV viral load, and HCV/HIV co-infection were the factors associated with an increased transmission risk.

In patients with chronic hepatitis C (HCV) infection, the strongest predictors of increased transmission risk — as evidenced by higher molecular clustering frequencies — were younger age, human immunodeficiency virus (HIV) co-infection, and an elevated HCV viral load, according to study results published in the Journal of Viral Hepatitis.

Examination of viral sequences using molecular epidemiologic analysis to detect genetic clustering frequencies can help identify the factors that are most associated with an elevated risk for viral transmission. Investigators assessed clustering frequencies among individuals chronically infected with HCV (genotypes 1 to 6) to determine which factors were most strongly linked to higher transmission risk.

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A large multicenter international (24 countries) dataset of HCV sequences from 7457 patients with chronic HCV (61.9% genotype 1; 60.6% North American; 94.7% HIV-negative) being treated with sofosbuvir plus ribavirin (as part of phase 2/3 trials) was analyzed for genetic clustering frequencies. From the patients, 3 strains of HCV were sequenced: NS34A (n=1605), NS5A (n=6462) and NS5B (n=6645). There was also a subset (n=211) of patients studied longitudinally to determine the appropriate genetic distance clustering threshold; receiver operator characteristic analysis revealed this to be 0.02 substitutions/site. Multivariate logistic regression modeling was used to determine the clinical and demographic factors associated with higher clustering frequencies and adjusted odds ratios (aORs) were calculated.

Of all patients, 541 (7.3%) were found to have increased clustering frequencies, representing 256 inferred clusters. Higher clustering frequency, ie, increased transmission risk, was most strongly correlated with younger (12-19 years) age (aOR 4.5; P <.05), elevated (>107) HCV viral load (aOR 1.3; P <.05), and HIV co-infection (aOR 2.1; P <.001). The 397 patients (5.3%) co-infected with HIV demonstrated a progressive effect of co-infection, whereby clustering with ≥2 other people raised the risk of transmission 3.02-fold compared with patients clustering with ≤1 person (P <.01).

Evaluation of only genotype 1 — present in 362/397 patients (91.2%) who were HIV-positive — showed associations between clustering and increased viral loads (P <.05) and HIV co-infection (P <.001), but not age. Sensitivity analysis demonstrated the 3 main associations detected to be generally robust.

The investigators concluded by noting, “…our results suggest that patients with HCV/HIV co-infection may disproportionately be the source of new HCV infections and treatment efforts should be geared towards elimination in this vulnerable population.” They recommended that future research focus on the differential effect of HIV co-infection across HCV transmission modes.

Disclosures: MRC, RH, and JOW were supported by a research grant to their institution from Gilead Sciences. JOW was also supported in part by an NIH-NIAID K01 Career Development Award (K01AI110181) and an NIH-NIAID R01 (AI136056).

There were no conflicts of interest declared.


Ragonnet‐Cronin M, Hostager R, Hedskog C, Osinusi A, Svarovskaia E, Wertheim JO. HIV co‐infection is associated with increased transmission risk in patients with chronic hepatitis C virus [pubished online June 13, 2019]. J Viral Hepat. doi:10.1111/jvh.13160