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 Mocrofta, M. Losso, M. Kundro, N. Vetter, R. Zangerle, I. Karpov, A. Vassilenko, V. M. Mitsura, D. PadutoN. Clumeck, S. De Wit, M. Delforge, E. Florence, L. Vandekerckhove, V. Hadziosmanovic, K. Kostov, J. Begovac, L. Machala, D. Jilich, D. Sedlacek, J. Nielsen, G. Kronborg, T. Benfield, M. Larsen, J. Gerstoft, T. Katzenstein, A. B E Hansen, P. Skinhøj, C. Pedersen, N. F. Møller, L. Ostergaard, U. B. Dragsted, L. N. Nielsen, K. Zilmer, Jelena Smidt, M. Ristola, C. Katlama, J. P. Viard, P. M. Girard, P. Vanhems, C. Pradier, F. Dabis, D. Neau, C. Duvivier, J. Rockstroh, R. Schmidt, J. Van Lunzen, O. Degen, H. J. Stellbrink, C. Stefan, J. Bogner, G. Fätkenheuer, N. Chkhartishvili, J. Kosmidis, P. Gargalianos, G. Xylomenos, J. Perdios, H. Sambatakou, D. Banhegyi, M. Gottfredsson, F. Mulcahy, I. Yust, D. Turner, M. Burke, E. Shahar, G. Hassoun, H. Elinav, M. Haouzi, Z. M. Sthoeger, A. D arminio Monforte, R. Esposito, I. Mazeu, C. Mussini, R. Pristera, F. Mazzotta, A. Gabbuti, V. Vullo, M. Lichtner, M. Zaccarelli, A. Antinori, R. Acinapura, G. D'Offizi, A. Lazzarin, A. Castagna, N. Gianotti, M. Galli, A. Ridolfo, B. Rozentale, V. Uzdaviniene, T. Staub, R. Hemmer, P. Reiss, V. Ormaasen, A. Maeland, J. Bruun, B. Knysz, J. Gasiorowski, M. Inglot, A. Horban, E. Bakowska, A. Grzeszczuk, R. Flisiak, M. Parczewski, M. Pynka, K. Maciejewska, M. Beniowski, E. Mularska, T. Smiatacz, E. Jablonowska, E. Malolepsza, K. Wojcik, I. Mozer-Lisewska, M. Doroana, L. Caldeira, K. Mansinho, F. Maltez, R. Radoi, C. Oprea, Victor Babes, A. Rakhmanova, A. Rakhmanova, T. Trofimora, I. Khromova, E. Kuzovatova, D. Jevtovic, A. Shunnar, D. Staneková, J. Tomazic, S. Moreno, J. M. Rodriguez, B. Clotet, A. Jou, R. Paredes, C. Tural, J. Puig, I. Bravo, J. M. Gatell, J. M. Miró, P. Domingo, M. Gutierrez, G. Mateo, M. A. Sambeat, J. M. Laporte, A. Blaxhult, L. Flamholc, A. Thalme, A. Sonnerborg, B. Ledergerber, R. Weber, M. Cavassini, A. Calmy, H. Furrer, M. Battegay, L. Elzi, P. Schmid, E. Kravchenko, N. Chentsova, V. Frolov, G. Kutsyna, I. Baskakov, S. Servitskiy, A. Kuznetsova, G. Kyselyova, B. Gazzard, A. M. Johnson, E. Simons, S. Edwards, A. Phillips, M. A. Johnson, A. Mocroft, C. Orkin, J. Weber, G. Scullard, M. Fisher, C. Leen

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 adjustedCoxmodels, risk factors for LRDincluded F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95%confidence interval (CI)4.1'9.6; andsHR2.5, 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 (sHR2.2%, 95%CI 1.7''2.9), but substantial in those withF2/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.

Original languageEnglish
Pages (from-to)1205-1215
Number of pages11
JournalAIDS (London, England)
Volume29
Issue number10
DOIs
Publication statusPublished - Jun 19 2015

Fingerprint

Hepacivirus
Antiviral Agents
HIV
Confidence Intervals
Fibrosis
Liver
CD4 Lymphocyte Count
Hepatitis B Surface Antigens
Cause of Death
Hepatitis C Antibodies
Mortality
Poisons
Virus Diseases
Therapeutics
Proportional Hazards Models
Health Care Costs
Names
Incidence
Population

Keywords

  • Causes of death
  • Directly acting antivirals
  • HIV/HCV co-infection
  • Liver fibrosis
  • Liver-related death

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

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.; Mocrofta, Amanda; Losso, M.; Kundro, M.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Jilich, D.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A. B E; Skinhøj, P.; Pedersen, C.; Møller, N. F.; Ostergaard, L.; Dragsted, U. B.; Nielsen, L. N.; Zilmer, K.; Smidt, Jelena; Ristola, M.; Katlama, C.; Viard, J. P.; Girard, P. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Duvivier, C.; Rockstroh, J.; Schmidt, R.; Van Lunzen, J.; Degen, O.; Stellbrink, H. J.; Stefan, C.; Bogner, J.; Fätkenheuer, G.; Chkhartishvili, N.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Sambatakou, H.; Banhegyi, D.; Gottfredsson, M.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Shahar, E.; Hassoun, G.; Elinav, H.; Haouzi, M.; Sthoeger, Z. M.; Monforte, A. D arminio; Esposito, R.; Mazeu, I.; Mussini, C.; Pristera, R.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Zaccarelli, M.; Antinori, A.; Acinapura, R.; D'Offizi, G.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Uzdaviniene, V.; Staub, T.; Hemmer, R.; Reiss, P.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Horban, A.; Bakowska, E.; Grzeszczuk, A.; Flisiak, R.; Parczewski, M.; Pynka, M.; Maciejewska, K.; Beniowski, M.; Mularska, E.; Smiatacz, T.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Mozer-Lisewska, I.; Doroana, M.; Caldeira, L.; Mansinho, K.; Maltez, F.; Radoi, R.; Oprea, C.; Babes, Victor; Rakhmanova, A.; Rakhmanova, A.; Trofimora, T.; Khromova, I.; Kuzovatova, E.; Jevtovic, D.; Shunnar, A.; Staneková, D.; Tomazic, J.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miró, J. M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Laporte, J. M.; Blaxhult, A.; Flamholc, L.; Thalme, A.; Sonnerborg, A.; Ledergerber, B.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Elzi, L.; Schmid, P.; Kravchenko, E.; Chentsova, N.; Frolov, V.; Kutsyna, G.; Baskakov, I.; Servitskiy, S.; Kuznetsova, A.; Kyselyova, G.; Gazzard, B.; Johnson, A. M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M. A.; Mocroft, A.; Orkin, C.; Weber, J.; Scullard, G.; Fisher, M.; Leen, C.

In: AIDS (London, England), Vol. 29, No. 10, 19.06.2015, p. 1205-1215.

Research output: Contribution to journalArticle

Grint, D, Peters, L, Rockstroh, JK, Rakmanova, A, Trofimova, T, Lacombe, K, Karpov, I, Galli, M, Domingo, P, Kirk, O, Lundgren, JD, Mocrofta, A, Losso, M, Kundro, M, Vetter, N, Zangerle, R, Karpov, I, Vassilenko, A, Mitsura, VM, Paduto, D, Clumeck, N, De Wit, S, Delforge, M, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Kostov, K, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Nielsen, J, Kronborg, G, Benfield, T, Larsen, M, Gerstoft, J, Katzenstein, T, Hansen, ABE, Skinhøj, P, Pedersen, C, Møller, NF, Ostergaard, L, Dragsted, UB, Nielsen, LN, Zilmer, K, Smidt, J, Ristola, M, Katlama, C, Viard, JP, Girard, PM, Vanhems, P, Pradier, C, Dabis, F, Neau, D, Duvivier, C, Rockstroh, J, Schmidt, R, Van Lunzen, J, Degen, O, Stellbrink, HJ, Stefan, C, Bogner, J, Fätkenheuer, G, Chkhartishvili, N, Kosmidis, J, Gargalianos, P, Xylomenos, G, Perdios, J, Sambatakou, H, Banhegyi, D, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Sthoeger, ZM, Monforte, ADA, Esposito, R, Mazeu, I, Mussini, C, Pristera, R, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, D'Offizi, G, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Staub, T, Hemmer, R, Reiss, P, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Horban, A, Bakowska, E, Grzeszczuk, A, Flisiak, R, Parczewski, M, Pynka, M, Maciejewska, K, Beniowski, M, Mularska, E, Smiatacz, T, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer-Lisewska, I, Doroana, M, Caldeira, L, Mansinho, K, Maltez, F, Radoi, R, Oprea, C, Babes, V, Rakhmanova, A, Rakhmanova, A, Trofimora, T, Khromova, I, Kuzovatova, E, Jevtovic, D, Shunnar, A, Staneková, D, Tomazic, J, Moreno, S, Rodriguez, JM, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gatell, JM, Miró, JM, Domingo, P, Gutierrez, M, Mateo, G, Sambeat, MA, Laporte, JM, Blaxhult, A, Flamholc, L, Thalme, A, Sonnerborg, A, Ledergerber, B, Weber, R, Cavassini, M, Calmy, A, Furrer, H, Battegay, M, Elzi, L, Schmid, P, Kravchenko, E, Chentsova, N, Frolov, V, Kutsyna, G, Baskakov, I, Servitskiy, S, Kuznetsova, A, Kyselyova, G, Gazzard, B, Johnson, AM, Simons, E, Edwards, S, Phillips, A, Johnson, MA, Mocroft, A, Orkin, C, Weber, J, Scullard, G, Fisher, M & Leen, C 2015, 'Liver-related death among HIV/hepatitis C virus-co-infected individuals: Implications for the era of directly acting antivirals', AIDS (London, England), vol. 29, no. 10, pp. 1205-1215. https://doi.org/10.1097/QAD.0000000000000674
Grint, Daniel ; Peters, Lars ; Rockstroh, Juergen K. ; Rakmanova, Aza ; Trofimova, Tatiana ; Lacombe, Karine ; Karpov, Igor ; Galli, Massimo ; Domingo, Pere ; Kirk, Ole ; Lundgren, Jens D. ; Mocrofta, Amanda ; Losso, M. ; Kundro, M. ; Vetter, N. ; Zangerle, R. ; Karpov, I. ; Vassilenko, A. ; Mitsura, V. M. ; Paduto, D. ; Clumeck, N. ; De Wit, S. ; Delforge, M. ; Florence, E. ; Vandekerckhove, L. ; Hadziosmanovic, V. ; Kostov, K. ; Begovac, J. ; Machala, L. ; Jilich, D. ; Sedlacek, D. ; Nielsen, J. ; Kronborg, G. ; Benfield, T. ; Larsen, M. ; Gerstoft, J. ; Katzenstein, T. ; Hansen, A. B E ; Skinhøj, P. ; Pedersen, C. ; Møller, N. F. ; Ostergaard, L. ; Dragsted, U. B. ; Nielsen, L. N. ; Zilmer, K. ; Smidt, Jelena ; Ristola, M. ; Katlama, C. ; Viard, J. P. ; Girard, P. M. ; Vanhems, P. ; Pradier, C. ; Dabis, F. ; Neau, D. ; Duvivier, C. ; Rockstroh, J. ; Schmidt, R. ; Van Lunzen, J. ; Degen, O. ; Stellbrink, H. J. ; Stefan, C. ; Bogner, J. ; Fätkenheuer, G. ; Chkhartishvili, N. ; Kosmidis, J. ; Gargalianos, P. ; Xylomenos, G. ; Perdios, J. ; Sambatakou, H. ; Banhegyi, D. ; Gottfredsson, M. ; Mulcahy, F. ; Yust, I. ; Turner, D. ; Burke, M. ; Shahar, E. ; Hassoun, G. ; Elinav, H. ; Haouzi, M. ; Sthoeger, Z. M. ; Monforte, A. D arminio ; Esposito, R. ; Mazeu, I. ; Mussini, C. ; Pristera, R. ; Mazzotta, F. ; Gabbuti, A. ; Vullo, V. ; Lichtner, M. ; Zaccarelli, M. ; Antinori, A. ; Acinapura, R. ; D'Offizi, G. ; Lazzarin, A. ; Castagna, A. ; Gianotti, N. ; Galli, M. ; Ridolfo, A. ; Rozentale, B. ; Uzdaviniene, V. ; Staub, T. ; Hemmer, R. ; Reiss, P. ; Ormaasen, V. ; Maeland, A. ; Bruun, J. ; Knysz, B. ; Gasiorowski, J. ; Inglot, M. ; Horban, A. ; Bakowska, E. ; Grzeszczuk, A. ; Flisiak, R. ; Parczewski, M. ; Pynka, M. ; Maciejewska, K. ; Beniowski, M. ; Mularska, E. ; Smiatacz, T. ; Jablonowska, E. ; Malolepsza, E. ; Wojcik, K. ; Mozer-Lisewska, I. ; Doroana, M. ; Caldeira, L. ; Mansinho, K. ; Maltez, F. ; Radoi, R. ; Oprea, C. ; Babes, Victor ; Rakhmanova, A. ; Rakhmanova, A. ; Trofimora, T. ; Khromova, I. ; Kuzovatova, E. ; Jevtovic, D. ; Shunnar, A. ; Staneková, D. ; Tomazic, J. ; Moreno, S. ; Rodriguez, J. M. ; Clotet, B. ; Jou, A. ; Paredes, R. ; Tural, C. ; Puig, J. ; Bravo, I. ; Gatell, J. M. ; Miró, J. M. ; Domingo, P. ; Gutierrez, M. ; Mateo, G. ; Sambeat, M. A. ; Laporte, J. M. ; Blaxhult, A. ; Flamholc, L. ; Thalme, A. ; Sonnerborg, A. ; Ledergerber, B. ; Weber, R. ; Cavassini, M. ; Calmy, A. ; Furrer, H. ; Battegay, M. ; Elzi, L. ; Schmid, P. ; Kravchenko, E. ; Chentsova, N. ; Frolov, V. ; Kutsyna, G. ; Baskakov, I. ; Servitskiy, S. ; Kuznetsova, A. ; Kyselyova, G. ; Gazzard, B. ; Johnson, A. M. ; Simons, E. ; Edwards, S. ; Phillips, A. ; Johnson, M. A. ; Mocroft, A. ; Orkin, C. ; Weber, J. ; Scullard, G. ; Fisher, M. ; Leen, C. / Liver-related death among HIV/hepatitis C virus-co-infected individuals : Implications for the era of directly acting antivirals. In: AIDS (London, England). 2015 ; Vol. 29, No. 10. pp. 1205-1215.
@article{1045e6552b394133a5a5e8131efc32eb,
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 adjustedCoxmodels, risk factors for LRDincluded F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95{\%}confidence interval (CI)4.1'9.6; andsHR2.5, 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 (sHR2.2{\%}, 95{\%}CI 1.7''2.9), but substantial in those withF2/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.",
keywords = "Causes of death, Directly acting antivirals, HIV/HCV co-infection, Liver fibrosis, Liver-related death",
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 Mocrofta and M. Losso and M. Kundro and N. Vetter and R. Zangerle and I. Karpov and A. Vassilenko and Mitsura, {V. M.} and D. Paduto and N. Clumeck and {De Wit}, S. and M. Delforge and E. Florence and L. Vandekerckhove and V. Hadziosmanovic and K. Kostov and J. Begovac and L. Machala and D. Jilich and D. Sedlacek and J. Nielsen and G. Kronborg and T. Benfield and M. Larsen and J. Gerstoft and T. Katzenstein and Hansen, {A. B E} and P. Skinh{\o}j and C. Pedersen and M{\o}ller, {N. F.} and L. Ostergaard and Dragsted, {U. B.} and Nielsen, {L. N.} and K. Zilmer and Jelena Smidt and M. Ristola and C. Katlama and Viard, {J. P.} and Girard, {P. M.} and P. Vanhems and C. Pradier and F. Dabis and D. Neau and C. Duvivier and J. Rockstroh and R. Schmidt and {Van Lunzen}, J. and O. Degen and Stellbrink, {H. J.} and C. Stefan and J. Bogner and G. F{\"a}tkenheuer and N. Chkhartishvili and J. Kosmidis and P. Gargalianos and G. Xylomenos and J. Perdios and H. Sambatakou and D. Banhegyi and M. Gottfredsson and F. Mulcahy and I. Yust and D. Turner and M. Burke and E. Shahar and G. Hassoun and H. Elinav and M. Haouzi and Sthoeger, {Z. M.} and Monforte, {A. D arminio} and R. Esposito and I. Mazeu and C. Mussini and R. Pristera and F. Mazzotta and A. Gabbuti and V. Vullo and M. Lichtner and M. Zaccarelli and A. Antinori and R. Acinapura and G. D'Offizi and A. Lazzarin and A. Castagna and N. Gianotti and M. Galli and A. Ridolfo and B. Rozentale and V. Uzdaviniene and T. Staub and R. Hemmer and P. Reiss and V. Ormaasen and A. Maeland and J. Bruun and B. Knysz and J. Gasiorowski and M. Inglot and A. Horban and E. Bakowska and A. Grzeszczuk and R. Flisiak and M. Parczewski and M. Pynka and K. Maciejewska and M. Beniowski and E. Mularska and T. Smiatacz and E. Jablonowska and E. Malolepsza and K. Wojcik and I. Mozer-Lisewska and M. Doroana and L. Caldeira and K. Mansinho and F. Maltez and R. Radoi and C. Oprea and Victor Babes and A. Rakhmanova and A. Rakhmanova and T. Trofimora and I. Khromova and E. Kuzovatova and D. Jevtovic and A. Shunnar and D. Stanekov{\'a} and J. Tomazic and S. Moreno and Rodriguez, {J. M.} and B. Clotet and A. Jou and R. Paredes and C. Tural and J. Puig and I. Bravo and Gatell, {J. M.} and Mir{\'o}, {J. M.} and P. Domingo and M. Gutierrez and G. Mateo and Sambeat, {M. A.} and Laporte, {J. M.} and A. Blaxhult and L. Flamholc and A. Thalme and A. Sonnerborg and B. Ledergerber and R. Weber and M. Cavassini and A. Calmy and H. Furrer and M. Battegay and L. Elzi and P. Schmid and E. Kravchenko and N. Chentsova and V. Frolov and G. Kutsyna and I. Baskakov and S. Servitskiy and A. Kuznetsova and G. Kyselyova and B. Gazzard and Johnson, {A. M.} and E. Simons and S. Edwards and A. Phillips and Johnson, {M. A.} and A. Mocroft and C. Orkin and J. Weber and G. Scullard and M. Fisher and C. Leen",
year = "2015",
month = "6",
day = "19",
doi = "10.1097/QAD.0000000000000674",
language = "English",
volume = "29",
pages = "1205--1215",
journal = "AIDS",
issn = "0269-9370",
publisher = "NLM (Medline)",
number = "10",

}

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 - Mocrofta, Amanda

AU - Losso, M.

AU - Kundro, M.

AU - Vetter, N.

AU - Zangerle, R.

AU - Karpov, I.

AU - Vassilenko, A.

AU - Mitsura, V. M.

AU - Paduto, D.

AU - Clumeck, N.

AU - De Wit, S.

AU - Delforge, M.

AU - Florence, E.

AU - Vandekerckhove, L.

AU - Hadziosmanovic, V.

AU - Kostov, K.

AU - Begovac, J.

AU - Machala, L.

AU - Jilich, D.

AU - Sedlacek, D.

AU - Nielsen, J.

AU - Kronborg, G.

AU - Benfield, T.

AU - Larsen, M.

AU - Gerstoft, J.

AU - Katzenstein, T.

AU - Hansen, A. B E

AU - Skinhøj, P.

AU - Pedersen, C.

AU - Møller, N. F.

AU - Ostergaard, L.

AU - Dragsted, U. B.

AU - Nielsen, L. N.

AU - Zilmer, K.

AU - Smidt, Jelena

AU - Ristola, M.

AU - Katlama, C.

AU - Viard, J. P.

AU - Girard, P. M.

AU - Vanhems, P.

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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 adjustedCoxmodels, risk factors for LRDincluded F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95%confidence interval (CI)4.1'9.6; andsHR2.5, 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 (sHR2.2%, 95%CI 1.7''2.9), but substantial in those withF2/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 adjustedCoxmodels, risk factors for LRDincluded F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95%confidence interval (CI)4.1'9.6; andsHR2.5, 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 (sHR2.2%, 95%CI 1.7''2.9), but substantial in those withF2/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.

KW - Causes of death

KW - Directly acting antivirals

KW - HIV/HCV co-infection

KW - Liver fibrosis

KW - Liver-related death

UR - http://www.scopus.com/inward/record.url?scp=84938990344&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938990344&partnerID=8YFLogxK

U2 - 10.1097/QAD.0000000000000674

DO - 10.1097/QAD.0000000000000674

M3 - Article

C2 - 25870984

AN - SCOPUS:84938990344

VL - 29

SP - 1205

EP - 1215

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 10

ER -