Risk of hepatitis C reinfection following successful therapy among people living with HIV: A global systematic review, meta-analysis, and meta-regression

Background: The benefits of direct-acting antivirals towards the elimination of hepatitis C virus (HCV) in people living with HIV are decreased when individuals are reinfected with HCV following treatment. We aimed to systematically review the existing evidence of HCV reinfection risk after treatment among people living with HIV, including people who inject drugs and men who have sex with men (MSM), and to identify the factors that explain heterogeneity in the incidence of HCV reinfection.

Methods: For this systematic review and meta-analysis, we searched PubMed, Scopus, Web of Science, Cochrane, PsycINFO, and conference presentations from date of database inception to Jan 10, 2022, for clinical trials and cohort studies providing data that could be used to calculate the incidence of HCV reinfection following HCV treatment. Random-effect meta-analysis models were used to calculate rate estimates. Study-level factors contributing to heterogeneity of reinfection estimates were assessed using meta-regression. This study is registered with PROSPERO, CRD42019146973.

Findings: 41 studies, predominantly conducted in Europe, were included, with a total of 9024 participants. The incidence of reinfection was 3.76 cases per 100 person-years of follow-up (95% CI 2.80–5.05; I² 85.9%) among people living with HIV overall, 6.01 (4.54–7.95; 74.1%) among MSM, and 3.29 (2.01–5.39; 83.9%) among people who inject drugs. A similar incidence of reinfection was observed following interferon-based therapy (4.92 cases per 100 person-years of follow-up, 3.30–7.32; I² 78.3%) and direct-acting antiviral therapy (3.88, 2.51–6.01; 85.4%). A higher proportion (≥85%) of MSM in the study population (adjusted rate ratio 2.66, 95% CI 1.37–5.15) and recent HCV infection (2.22, 1.09–4.55) were associated with an increased incidence of reinfection; a longer duration of follow-up after treatment (0.97, 0.96–0.99) was associated with a decreased incidence.

Interpretation: Risk of HCV reinfection following treatment in people living with HIV was highest among MSM and those with recent HCV infection. Continued scale-up of HCV treatment and ongoing HCV screening and treatment of infection in this patient population should reduce viraemic burden and risk of reinfection.

• Epidemiology and Determinants of Health
  • Epidemiology
• Population(s)
  • General HIV+ population
• Prevention, Engagement and Care Cascade
  • Engagement and Care Cascade
• Engagement and Care Cascade
  • Treatment
• Co-infections
  • Hepatitis B, C