Direct, indirect and total effect of HIV coinfection on the risk of non-liver-related cancer in hepatitis C virus-infected patients treated by direct-acting antivirals: a mediation analysis

Mathieu Chalouni (1, 2) , Stanislas Pol (3, 4, 5) , Philippe Sogni (3, 4, 5) , Helene Fontaine (3, 4) , Karine Lacombe (6, 7) , Jean-Marc Lacombe (8) , Laure Esterle (1) , Celine Dorival (6) , Marc Bourliere (9) , Firouze Bani-Sadr (10) , Victor de Ledinghen (11, 12) , David Zucman (13) , Dominique Larrey (14, 15) , Dominique Salmon (5, 4) , Fabrice Carrat (6, 7) , Linda Wittkop (1, 11) , Anrs C. O. Hepather Cohorts Study Groups Anrs Co13 Hepavih , V. Martinez

1 INSERM U1219 - UB - ISPED - Team MORPH3EUS
2 BPH - Bordeaux population health
3 Inserm U1223 - Physiopathologie du système immunitaire
4 Hôpital Cochin [AP-HP]
5 UPCité - Université Paris Cité
6 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
7 CHU Saint-Antoine [AP-HP]
8 IT - INSERM-TRANSFERT [Paris]
9 Hôpital Saint-Joseph [Marseille]
10 Hôpital Robert Debré
11 CHU Bordeaux
12 BaRITOn - Bordeaux Research In Translational Oncology [Bordeaux]
13 Hôpital Foch [Suresnes]
14 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
15 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)

OBJECTIVES: HIV-coinfected patients experience higher incidences of non-liver-related cancers than HCV-monoinfected patients. Chronic inflammation, immunosuppression, but also higher tobacco or alcohol consumption and metabolic dysregulation could explain this higher risk. We aimed to estimate the direct, indirect and total effects of HIV coinfection on the risk of non-liver-related cancers in HCV participants treated with direct-acting antivirals (DAAs). METHODS: Up to four HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to HIV/HCV-coinfected participants from the ANRS CO13 HEPAVIH cohort. Participants were followed from DAA initiation until the occurrence of a non-liver-related cancer. Counterfactual mediation analysis was carried out to estimate the direct (chronic inflammation and immunosuppression), indirect (tobacco and alcohol consumption and metabolic syndrome) and total effect of HIV coinfection on the risk of non-liver-related cancers. RESULTS: 548 HIV/HCV-coinfected and 2016 monoinfected participants were included. Overall, HIV coinfection was associated with a 3.7-fold [95% confidence interval (CI): 1.7-7.0] higher risk of non-liver-related cancers in HCV participants. This increased risk was explained by significant direct effect [hazard ratio (HR) = 3.4, 95% CI: 1.7-6.6] but not indirect effect (HR = 1.1, 95% CI: 0.8-1.5) of HIV coinfection. CONCLUSIONS: In HCV participants treated with DAAs, the direct effect of HIV coinfection, reflecting chronic inflammation and immunosuppression, was associated with a 3.7-fold higher risk of non-liver-related cancer. By contrast, the indirect effect of HIV coinfection, reflecting higher tobacco and alcohol consumption and metabolic dysregulation, was not significantly associated with the risk of non-liver-related cancers.

Mots clés: Non-liver-related cancers; Mediation analysis; HIV coinfection; HCV; Direct-acting antiviral (DAA) treatment; direct-acting antiviral (DAA) treatment; mediation analysis; non-liver-related cancers

Domaines: Santé publique et épidémiologie

Mathieu Chalouni, Stanislas Pol, Philippe Sogni, Helene Fontaine, Karine Lacombe, et al.. Direct, indirect and total effect of HIV coinfection on the risk of non-liver-related cancer in hepatitis C virus-infected patients treated by direct-acting antivirals: a mediation analysis. HIV Medicine, 2021, 22 (10), pp.924-935. ⟨10.1111/hiv.13153⟩. ⟨hal-03361010⟩