Increased mortality in HIV/HCV-coinfected compared to HCV-monoinfected patients in the DAA era due to non-liver-related death

Mathieu Chalouni; Stanislas Pol; Philippe Sogni; Hélène Fontaine; Karine Lacombe; Jean Marc-Lacombe; Laure Esterle; Celine Dorival; Marc Bourlière; Firouzé Bani-Sadr; Victor de Ledinghen; David Zucman; Dominique Larrey; Dominique Salmon; Fabrice Carrat; Linda Wittkop; ANRS CO13 HEPAVIH and ANRS CO22 HEPATHER cohort study groups

doi:10.1016/j.jhep.2020.08.008

Increased mortality in HIV/HCV-coinfected compared to HCV-monoinfected patients in the DAA era due to non-liver-related death

J Hepatol. 2021 Jan;74(1):37-47. doi: 10.1016/j.jhep.2020.08.008. Epub 2020 Aug 14.

Authors

Mathieu Chalouni¹, Stanislas Pol², Philippe Sogni², Hélène Fontaine², Karine Lacombe³, Jean Marc-Lacombe⁴, Laure Esterle¹, Celine Dorival⁵, Marc Bourlière⁶, Firouzé Bani-Sadr⁷, Victor de Ledinghen⁸, David Zucman⁹, Dominique Larrey¹⁰, Dominique Salmon¹¹, Fabrice Carrat¹², Linda Wittkop¹³; ANRS CO13 HEPAVIH and ANRS CO22 HEPATHER cohort study groups

Collaborators

ANRS CO13 HEPAVIH and ANRS CO22 HEPATHER cohort study groups:
D Salmon, L Wittkop, P Sogni, L Esterle, P Trimoulet, J Izopet, L Serfaty, V Paradis, B Spire, P Carrieri, M A Valantin, G Pialoux, J Chas, I Poizot-Martin, K Barange, A Naqvi, E Rosenthal, A Bicart-See, O Bouchaud, A Gervais, C Lascoux-Combe, C Goujard, K Lacombe, C Duvivier, D Neau, P Morlat, F Bani-Sadr, L Meyer, F Boufassa, B Autran, A M Roque, C Solas, H Fontaine, D Costagliola, L Piroth, A Simon, D Zucman, F Boué, P Miailhes, E Billaud, H Aumaitre, D Rey, G Peytavin, V Petrov-Sanchez, D Lebrasseur-Longuet

Affiliations

¹ ISPED, INSERM, Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, CIC-EC 1401, University of Bordeaux, Bordeaux, France.
² Assistance Publique - Hôpitaux de Paris, Hôpital Cochin, Département d'Hépatologie, Université de Paris, INSERM U-1223 et ICD, Institut Pasteur, Paris, France.
³ INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, Paris, France; APHP, Hôpital Saint-Antoine, Service de Maladies Infectieuses et Tropicales, Paris, France.
⁴ INSERM Transfert, Paris, France.
⁵ INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, Paris, France.
⁶ Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France.
⁷ Department of Internal Medicine, Clinical Immunology and Infectious Diseases, Robert Debré Hospital, University Hospital, Reims, France.
⁸ Service d'Hépatologie, Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévêque, Bordeaux, France; INSERM U1053, Université de Bordeaux, Bordeaux, France.
⁹ Service de Médecine Interne, Hôpital Foch, Suresnes, France.
¹⁰ Service des Maladies de l'Appareil Digestif, Hôpital Saint Eloi, IBR - INSERM, Montpellier, France.
¹¹ Université de Paris, Paris, France; Service Maladies Infectieuses et Tropicales, AP-HP, Hôpital Cochin Hôtel Dieu, Paris, France.
¹² INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, Paris, France; AP-HP, Hôpital Saint-Antoine, Unité de Santé Publique, Paris, France.
¹³ ISPED, INSERM, Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, CIC-EC 1401, University of Bordeaux, Bordeaux, France; CHU de Bordeaux, Pôle de Santé Publique, Bordeaux, France. Electronic address: [email protected].

PMID: 32798585
DOI: 10.1016/j.jhep.2020.08.008

Abstract

Background & aims: Direct-acting antivirals (DAA) lead to high sustained virological response (SVR) rates and decrease the risk of disease progression. We compared SVR rates and all-cause, liver- and non-liver-related deaths, liver-related events, and non-liver-related cancers in HIV/HCV-coinfected and HCV-monoinfected participants from 2 French cohort studies after initiation of DAA treatment.

Methods: Up to 4 HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to each HIV/HCV-coinfected patient from the ANRS CO13 HEPAVIH cohort; both are nationwide, prospective, multicentre, and observational. Participants were initiated on DAAs between March 2014 and December 2017. Cox proportional hazards models adjusted by age, sex, duration since HCV diagnosis, HCV transmission routes, HCV genotypes, cirrhosis, tobacco, alcohol consumption, and SVR (time dependent) were used.

Results: A total of 592 HIV/HCV-coinfected and 2,049 HCV-monoinfected participants were included; median age was 53.3 years (inter-quartile range: 49.6-56.9) and 52.9 years (49.6; 56.7), 1,498 (73.1%) and 436 (73.6%) were men, and 159 (28.8%) and 793 (41.2%) had cirrhosis, respectively. SVR was observed in 92.9% and 94.6%, respectively. HIV coinfection was associated with higher risk of all-cause death (hazard ratio [HR] 1.93; 95% CI 1.01-3.69), non-liver-related death (HR 2.84; 95% CI 1.27-6.36), and non-liver-related cancer (HR 3.26; 95% CI 1.50-7.08), but not with liver-related-death (HR 1.04; 95% CI 0.34-3.15) or liver-related events (HR 0.66; 95% CI 0.31-1.44).

Conclusions: After DAA treatment, HIV-coinfected individuals had similar SVR rates and risk of liver-related deaths and events compared with HCV-monoinfected individuals, but had a higher risk of all-cause and non-liver-related deaths and non-liver-related cancers.

Lay summary: We compared the risk of several clinical events in participants infected by human immunodeficiency virus and hepatitis C virus with those infected with hepatitis C virus alone, matched on age and sex, after treatment with contemporary direct-acting antivirals. We found a higher risk of all-cause deaths, non-liver-related deaths, and non-liver-related cancers in participants coinfected with the human immunodeficiency virus and hepatitis C virus, and no differences for the risk of liver-related deaths or events.

Trial registration: ClinicalTrials.gov NCT03324633 NCT01953458.

Keywords: DAA treatment; Death; HIV coinfection; Liver-related events; Non-liver-related cancers; SVR.

Publication types

Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / administration & dosage
Cause of Death*
Disease Progression
Female
France / epidemiology
HIV Infections* / diagnosis
HIV Infections* / drug therapy
HIV Infections* / epidemiology
HIV* / drug effects
HIV* / isolation & purification
Hepacivirus* / drug effects
Hepacivirus* / genetics
Hepacivirus* / isolation & purification
Hepatitis C, Chronic* / diagnosis
Hepatitis C, Chronic* / drug therapy
Hepatitis C, Chronic* / epidemiology
Humans
Liver Cirrhosis / diagnosis
Liver Cirrhosis / epidemiology
Male
Middle Aged
Mortality / trends
Oligopeptides* / administration & dosage
Oligopeptides* / adverse effects
Proline / administration & dosage
Proline / adverse effects
Proline / analogs & derivatives*
Substance-Related Disorders / diagnosis
Substance-Related Disorders / epidemiology
Sustained Virologic Response

Substances

Antiviral Agents
Oligopeptides
telaprevir
N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
Proline

Associated data

ClinicalTrials.gov/NCT03324633
ClinicalTrials.gov/NCT01953458