Liver-related death among HIV/hepatitis C virus-co-infected individuals: implications for the era of directly acting antivirals

Daniel Grint, Lars Peters, Juergen K Rockstroh, Aza Rakmanova, Tatiana Trofimova, Karine Lacombe, Igor Karpov, Massimo Galli, Pere Domingo, Ole Kirk, Jens D Lundgren, Amanda Mocroft, EuroSIDA in EuroCoord, Court Pedersen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment.

METHODS: Three thousand, nine hundred and forty-one HCV antibody-positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow-up after 1 January 2000 were included, with causes of death classified using Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD.

RESULTS: LRD accounted for 145 of 670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI) 4.1-9.6; and sHR 2.5, 95% CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95% CI 0.73-0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI 1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively).

CONCLUSION: Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.

OriginalsprogEngelsk
TidsskriftAIDS
Vol/bind29
Udgave nummer10
Sider (fra-til)1205-15
Antal sider11
ISSN0269-9370
DOI
StatusUdgivet - 19. jun. 2015

Fingeraftryk

Hepacivirus
HIV
Confidence Intervals
Liver
Hepatitis B Surface Antigens
Proportional Hazards Models
Cause of Death
Hepatitis C Antibodies
Poisons
Virus Diseases
Names
Incidence
Population

Citer dette

Grint, Daniel ; Peters, Lars ; Rockstroh, Juergen K ; Rakmanova, Aza ; Trofimova, Tatiana ; Lacombe, Karine ; Karpov, Igor ; Galli, Massimo ; Domingo, Pere ; Kirk, Ole ; Lundgren, Jens D ; Mocroft, Amanda ; EuroSIDA in EuroCoord ; Pedersen, Court. / Liver-related death among HIV/hepatitis C virus-co-infected individuals : implications for the era of directly acting antivirals. I: AIDS. 2015 ; Bind 29, Nr. 10. s. 1205-15.
@article{32b39b6b1eb34c049bad40de0708e10b,
title = "Liver-related death among HIV/hepatitis C virus-co-infected individuals: implications for the era of directly acting antivirals",
abstract = "BACKGROUND: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment.METHODS: Three thousand, nine hundred and forty-one HCV antibody-positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow-up after 1 January 2000 were included, with causes of death classified using Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD.RESULTS: LRD accounted for 145 of 670 (21.6{\%}) deaths in the study population. LRD rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95{\%} confidence interval (CI) 4.1-9.6; and sHR 2.5, 95{\%} CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95{\%} CI 0.73-0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95{\%} CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2{\%}, 95{\%} CI 1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3{\%}, 95{\%} CI 7.6-13.5; and sHR 14.0{\%}, 95{\%} CI 10.3-18.3, respectively).CONCLUSION: Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.",
author = "Daniel Grint and Lars Peters and Rockstroh, {Juergen K} and Aza Rakmanova and Tatiana Trofimova and Karine Lacombe and Igor Karpov and Massimo Galli and Pere Domingo and Ole Kirk and Lundgren, {Jens D} and Amanda Mocroft and {EuroSIDA in EuroCoord} and Court Pedersen",
year = "2015",
month = "6",
day = "19",
doi = "10.1097/QAD.0000000000000674",
language = "English",
volume = "29",
pages = "1205--15",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams & Wilkins",
number = "10",

}

Grint, D, Peters, L, Rockstroh, JK, Rakmanova, A, Trofimova, T, Lacombe, K, Karpov, I, Galli, M, Domingo, P, Kirk, O, Lundgren, JD, Mocroft, A, EuroSIDA in EuroCoord & Pedersen, C 2015, 'Liver-related death among HIV/hepatitis C virus-co-infected individuals: implications for the era of directly acting antivirals', AIDS, bind 29, nr. 10, s. 1205-15. https://doi.org/10.1097/QAD.0000000000000674

Liver-related death among HIV/hepatitis C virus-co-infected individuals : implications for the era of directly acting antivirals. / Grint, Daniel; Peters, Lars; Rockstroh, Juergen K; Rakmanova, Aza; Trofimova, Tatiana; Lacombe, Karine; Karpov, Igor; Galli, Massimo; Domingo, Pere; Kirk, Ole; Lundgren, Jens D; Mocroft, Amanda; EuroSIDA in EuroCoord ; Pedersen, Court.

I: AIDS, Bind 29, Nr. 10, 19.06.2015, s. 1205-15.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Liver-related death among HIV/hepatitis C virus-co-infected individuals

T2 - implications for the era of directly acting antivirals

AU - Grint, Daniel

AU - Peters, Lars

AU - Rockstroh, Juergen K

AU - Rakmanova, Aza

AU - Trofimova, Tatiana

AU - Lacombe, Karine

AU - Karpov, Igor

AU - Galli, Massimo

AU - Domingo, Pere

AU - Kirk, Ole

AU - Lundgren, Jens D

AU - Mocroft, Amanda

AU - EuroSIDA in EuroCoord

AU - Pedersen, Court

PY - 2015/6/19

Y1 - 2015/6/19

N2 - BACKGROUND: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment.METHODS: Three thousand, nine hundred and forty-one HCV antibody-positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow-up after 1 January 2000 were included, with causes of death classified using Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD.RESULTS: LRD accounted for 145 of 670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI) 4.1-9.6; and sHR 2.5, 95% CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95% CI 0.73-0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI 1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively).CONCLUSION: Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.

AB - BACKGROUND: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment.METHODS: Three thousand, nine hundred and forty-one HCV antibody-positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow-up after 1 January 2000 were included, with causes of death classified using Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD.RESULTS: LRD accounted for 145 of 670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI) 4.1-9.6; and sHR 2.5, 95% CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95% CI 0.73-0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI 1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively).CONCLUSION: Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.

U2 - 10.1097/QAD.0000000000000674

DO - 10.1097/QAD.0000000000000674

M3 - Journal article

C2 - 25870984

VL - 29

SP - 1205

EP - 1215

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 10

ER -