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

Grint, D.; Peters, L.; Rockstroh, J. K.; Rakmanova, A.; Trofimova, T.; Lacombe, K.; Karpov, I.; Galli, M.; Domingo, P.; Kirk, O.; Lundgren, J. D.; Mocrofta, A.; 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.; Skinhoj, P.; Pedersen, C.; Moller, N. F.; Ostergaard, L.; Dragsted, U. B.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; 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.; Fatkenheuer, 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.; 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.; Stanekova, D.; Tomazic, J.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miro, 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.

doi:10.1097/QAD.0000000000000674

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.

Liver-related death among HIV/hepatitis C virus-co-infected individuals: Implications for the era of directly acting antivirals / Grint, D.; Peters, L.; Rockstroh, J. K.; Rakmanova, A.; Trofimova, T.; Lacombe, K.; Karpov, I.; Galli, M.; Domingo, P.; Kirk, O.; Lundgren, J. D.; Mocrofta, A.; 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.; Skinhoj, P.; Pedersen, C.; Moller, N. F.; Ostergaard, L.; Dragsted, U. B.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; 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.; Fatkenheuer, 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.; 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.; Stanekova, D.; Tomazic, J.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miro, 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. - ISSN 0269-9370. - 29:10(2015), pp. 1205-1215. [10.1097/QAD.0000000000000674]

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

Grint D.;Peters L.;Rockstroh J. K.;Rakmanova A.;Trofimova T.;Lacombe K.;Karpov I.;Galli M.;Domingo P.;Kirk O.;Lundgren J. D.;Mocrofta A.;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.;Skinhoj P.;Pedersen C.;Moller N. F.;Ostergaard L.;Dragsted U. B.;Nielsen L. N.;Zilmer K.;Smidt J.;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.;Fatkenheuer 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.;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.;Stanekova D.;Tomazic J.;Moreno S.;Rodriguez J. M.;Clotet B.;Jou A.;Paredes R.;Tural C.;Puig J.;Bravo I.;Gatell J. M.;Miro 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.

2015

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.

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	Anno di pubblicazione
	
				2015
			
	Rivista
	
				AIDS
			
	N° del Volume
	
				29
			
	Fascicolo
	
				10
			
	Pagina iniziale
	
				1205
			
	Pagina finale
	
				1215
			
	Codice DOI
	
				https://dx.doi.org/10.1097/QAD.0000000000000674
			
	Codice WoS
	
				WOS:000368481400003
			
	Codice Scopus
	
				2-s2.0-84938990344
			
	Codice PubMed
	
				25870984
			
	Citazione
	
				Liver-related death among HIV/hepatitis C virus-co-infected individuals: Implications for the era of directly acting antivirals / Grint, D.; Peters, L.; Rockstroh, J. K.; Rakmanova, A.; Trofimova, T.; Lacombe, K.; Karpov, I.; Galli, M.; Domingo, P.; Kirk, O.; Lundgren, J. D.; Mocrofta, A.; 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.; Skinhoj, P.; Pedersen, C.; Moller, N. F.; Ostergaard, L.; Dragsted, U. B.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; 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.; Fatkenheuer, 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.; 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.; Stanekova, D.; Tomazic, J.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miro, 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. - ISSN 0269-9370. - 29:10(2015), pp. 1205-1215. [10.1097/QAD.0000000000000674]
			
	Tutti gli autori
	
						Grint, D.; Peters, L.; Rockstroh, J. K.; Rakmanova, A.; Trofimova, T.; Lacombe, K.; Karpov, I.; Galli, M.; Domingo, P.; Kirk, O.; Lundgren, J. D.; Moc...espandi
						
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