Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection – The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index
June
Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection - The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index
Kathleen C. Rollet-Kurhajec 0 1
Erica E. M. Moodie 0 1
Sharon Walmsley 0 1
Curtis Cooper 0 1
Neora Pick 0 1
Marina B. Klein 0 1
Canadian Co-infection Cohort Study (CTN 0 1
0 1 Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, McGill University Health Centre , Montreal , Canada , 2 Department of Epidemiology & Biostatistics, McGill University , Montreal , Canada , 3 University Health Network , Toronto , Canada , 4 CIHR Canadian HIV Trials Network, Vancouver , Canada , 5 The Ottawa Hospital Research Institute , Ottawa , Canada , 6 Oak Tree Clinic, BC Women's Hospital, Divisions of Infectious Diseases, Department of Medicine, University of British Columbia , Vancouver , Canada
1 Academic Editor: Jason Blackard, University of Cincinnati College of Medicine, UNITED STATES
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Funding: This study was funded by the Fonds de
recherche en santé du Québec, Réseau SIDA/
maladies infectieuses (FRQ-S), the Canadian
In Hepatitis C virus (HCV) mono-infection, male sex is associated with faster liver fibrosis
progression but the effects of sex have not been well studied in HIV-HCV co-infected
patients. We examined the influence of sex on progression to significant liver fibrosis in
HIV-HCV co-infected adults receiving antiretroviral therapy (ART) using the aspartate
aminotransferase-to-platelet ratio index (APRI) as a surrogate biomarker of liver fibrosis.
We evaluated 308 HIV infected, HCV RNA positive participants of a Canadian multicentre
prospective cohort receiving antiretrovirals and without significant liver fibrosis or end-stage
liver disease at baseline. We used multivariate discrete-time proportional hazards models
to assess the effect of sex on time to significant fibrosis (APRI 1.5) adjusting for baseline
age, alcohol use, cigarette smoking, HCV duration, and APRI and time-updated CD4 count
Overall, 55 (18%) participants developed an APRI
1.5 over 544 person-years of at-risk
tional risk factors for liver disease progression (younger, shorter duration of HCV infection
Institutes of Health Research (CIHR MOP-79529)
and the CIHR Canadian HIV Trials Network
(CTN222). MBK is supported by a “Chercheurs
nationaux” career award from the FRQ-S. EEMM is
supported by a “chercheurs boursiers” career award
from FRQ-S. SW has a career award from the
Ontario HIV treatment Network. CC is supported by
The Ontario HIV Treatment Network (Applied HIV
Research Chair) and The Ottawa Hospital
Department of Medicine. The funders had no role in
study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
Competing Interests: MBK reports receipt of grants
to her institution from the Canadian Institute of Health
Research (CIHR), Fonds de recherches en santé du
Québec (FRQ-S) and CIHR Canadian HIV Trials
Network (CTN); research support from Merck and
Schering-Plough; board membership fees from the
CTN; consulting fees from ViiV, Abbvie and Gilead;
and honoraria for lectures from Janssen, ViiV and
Merck. CC reports receipt of consulting fees from
Merck and Vertex; honoraria for lectures from Merck
and Roche; previous grants to his institution from
Merck and Abbott; and funding support from The
Ottawa Hospital Department of Medicine. SW reports
receipt of grants to her institution from the CTN, Viiv
and Merck; board membership fees, consulting fees
and honoraria for lectures from Merck, Abbott, ViiV,
Gilead, BMS, Tibotec and Janssen. NP reports
receipt of grants to her institution from the CTN.
EEMM and KCR-K report no conflicts of interest. This
does not alter the authors' adherence to PLOS ONE
policies on sharing data and materials.
and less alcohol use). Despite this, female sex was associated with a greater than two-fold
increased risk of fibrosis progression (adjusted hazard rate (HR) =2.23; 1.22-4.08).
HIV-HCV co-infected women receiving antiretroviral therapy were at significantly greater
risk of progressing to liver fibrosis as measured by APRI compared with men. Enhanced
efforts to engage and treat co-infected women for HCV are needed.
Due to shared routes of transmission, hepatitis C virus (HCV) and HIV co-infection is
common. Approximately one quarter of HIV-infected Canadians are seropositive for HCV [1–2].
With improved outcomes on combination antiretroviral therapy (cART) AIDS related
mortality has declined significantly, yet liver-related morbidity and mortality has progressively
increased among co-infected patients [3–4] owing in part to more rapid hepatic fibrosis
progression [3, 5–6]. Residual HIV-related immune dysfunction [7–8], and immune activation,
cumulative cART induced hepatotoxicity [9] and metabolic changes are among the potential
causes of accelerated liver disease progression [10].
Worldwide women represent a rapidly growing segment of the HIV infected population
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