TY - JOUR

T1 - Clinical Outcomes in Persons Coinfected with Human Immunodeficiency Virus and Hepatitis C Virus

T2 - Impact of Hepatitis C Virus Treatment

AU - Mocroft, Amanda

AU - Lundgren, Jens

AU - Gerstoft, Jan

AU - Rasmussen, Line D.

AU - Bhagani, Sanjay

AU - Aho, Inka

AU - Pradier, Christian

AU - Bogner, Johannes R.

AU - Mussini, Christina

AU - Uberti Foppa, Caterina

AU - Maltez, Fernando

AU - Laguno, Montse

AU - Wandeler, Gilles

AU - Falconer, Karolin

AU - Trofimova, Tatyana

AU - Borodulina, Elena

AU - Jevtovic, Djordje

AU - Bakowska, Elzbieta

AU - Kase, Kerstin

AU - Kyselyova, Galina

AU - Haubrich, Richard

AU - Rockstroh, Jürgen K.

AU - Peters, Lars

AU - Losso, M.

AU - Schmied, B.

AU - Karpov, I.

AU - Clumeck, N.

AU - Hadziosmanovic, V.

AU - Begovac, J.

AU - Machala, L.

AU - Zilmer, K.

AU - Aho, I.

AU - Viard, J. P.

AU - Rockstroh, J.

AU - Chkhartishvili, N.

AU - Sambatakou, H.

AU - Szlávik, J.

AU - Gottfredsson, M.

AU - Mulcahy, F.

AU - Tau, L.

AU - D'Arminio Monforte, A.

AU - Rozentale, B.

AU - Uzdaviniene, V.

AU - Staub, T.

AU - Reiss, P.

AU - Reikvam, D. H.

AU - Knysz, B.

AU - Caldeira, L.

AU - Radoi, R.

AU - Panteleev, A.

AU - Dragovic, G.

AU - Tomazic, J.

AU - Miró, J. M.

AU - Falconer, K.

AU - Scherrer, A.

AU - Gazzard, B.

N1 - Funding Information: Financial support. This work was supported by the European Union’s Seventh Framework Programme for research, technological development, and demonstration (under European Coordinating Committee for the Integration of Ongoing Coordination Actions Related to Clinical and Epidemiological HIV Research [EuroCoord] grant agreement number 260694); unrestricted grants by ViiV Healthcare LLC, GlaxoSmithKline R&D Limited, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp, and Gilead Sciences; the Swiss National Science Foundation (grant number 148522); and the Danish National Research Foundation and the International Cohort Consortium of Infectious Disease (grant number DNRF126). Funding Information: Potential conflicts of interest. A. M. has received personal fees from ViiV and Gilead. S. B. has received personal fees from AbbVie and Gilead. I. A. has received personal fees from Gilead, Glaxo Smithkline (GSK), and Merck. C. P. has received personal fees from Gilead and Pfizer and nonfinancial support from VIIV Health Care and Merck, Sharp and Dohme (MSD). J. R. B. has received personal fees from AbbVie, Gilead, ViiV, Janssen, Hexal, Pfizer, Bristol Myers Squibb, and MSD. G. W. has received grants from Gilead Science and AbbVie outside the submitted work. K. K. has received personal fees from Estonian Government, MSD, and GSK and personal fees and other from Abbvie. R. H. is an employee of and stockholder in Gilead. J. K. R. has received personal fees from Abbvie, Gilead, Janssen, Merck, Siemens, and ViiV and personal fees from Abivax. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/5/15

Y1 - 2020/5/15

N2 - Background: A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear. Methods: People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD). Results: There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured. Conclusions: Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining he importance of successful HCV treatment for reducing ESLD.

AB - Background: A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear. Methods: People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD). Results: There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured. Conclusions: Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining he importance of successful HCV treatment for reducing ESLD.

KW - cardiovascular disease

KW - end-stage liver disease

KW - hepatitis C

KW - HIV

KW - malignancies

KW - EVENTS

KW - RISK

KW - DEATH

KW - HIV-INFECTION

KW - CARDIOVASCULAR-DISEASE

KW - MALIGNANCIES

KW - ERADICATION

KW - ASSOCIATION

UR - http://www.scopus.com/inward/record.url?scp=85084271418&partnerID=8YFLogxK

U2 - 10.1093/cid/ciz601

DO - 10.1093/cid/ciz601

M3 - Article

C2 - 31504296

AN - SCOPUS:85084271418

VL - 70

SP - 2131

EP - 2140

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 10

ER -