Hepatitis C virus reinfection following antiviral treatment among people who inject drugs: a systematic review and meta-analysis

Background: Among individuals with ongoing injecting drug use (IDU), HCV reinfection following successful therapy can compromise treatment outcome. This systematic review assessed HCV reinfection rate after treatment among people with recent IDU and those receiving opioid substitution therapy (OST).

Methods: Bibliographic databases and conference abstracts were searched for studies assessing HCV reinfection rate after treatment among people with recent IDU or those receiving OST. Meta-analysis was used to cumulate reinfection rates and meta-regression to explore factors associated with heterogeneity across studies.

Results: Twenty-two eligible studies were included [total person-years follow-up (PYFU)=5112], including sub-population data of people with recent IDU (19 studies, PYFU=4116) and people receiving OST (11 studies, PYFU=1905). Recent IDU definition varied across studies (IDU during HCV treatment or post-treatment follow-up most commonly used). HCV reinfection rate was 5.4 per 100 PYFU (95%CI: 3.2, 8.9) among people with recent IDU, and 2.7 per 100 PYFU (95%CI: 1.4, 5.4) among those receiving OST. Reinfection rate was comparable between post-interferon-containing therapy (4.6 per 100 PYFU; 95%CI: 2.4, 8.8), and post-DAA therapy (3.4 per 100 PYFU; 95%CI: 2.3, 5.1). In stratified analysis, reinfection rate was 1.3 per 100 PYFU (95%CI: 0.5, 3.2) among people receiving OST with no recent IDU, 3.6 per 100 PYFU (95%CI: 1.5, 9.1) among those with recent IDU who also received OST, and 4.6 per 100 PYFU (95%CI: 2.1, 10.3) among those with recent IDU, not receiving OST. In adjusted meta-regression analysis, longer follow-up was significantly associated with lower reinfection rate [adjusted Rate Ratio (aRR) for each year increase in mean/median follow-up: 0.79 (95%CI: 0.67, 0.92; P=0.005), while using end of treatment as the start point of time-at-risk of reinfection, compared to 12 weeks post-treatment (SVR12) or later, was significantly associated with higher reinfection rate (aRR: 2.54 (1.28, 5.04; P=0.011). Diagnosis of reinfection following end of treatment was based on virus sequencing data, or genotype-switch.

Conclusion: Post-treatment HCV reinfection rate was the highest among people with recent IDU, not receiving OST. Higher rate in studies assessing reinfection from the end of treatment and lower rate in studies with longer follow-up suggested higher risk of reinfection early post-treatment. Harm reduction services are required to reduce the reinfection risk while regular post-treatment HCV assessment is required to detect and treat reinfection early.