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A longitudinal analysis of liver fibrosis progression among NNRTI and PI users in the
Canadian co-infection cohort study
Laurence Brunet,Erica E. M. Moodie, Jim Young,Sharon
Walmsley, Mark Hull, Curtis Cooper, Marina B. Klein
IAS 201521 July 2015
Background
HIV-HCV co-infection 20-30% of HIV+ are co-infected
HCV can be cured Only effective intervention to prevent liver
disease progression Very few have access to treatment
Combination antiretroviral therapy (cART) Used by majority Life-long treatment
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ART and the liver Studies are limited
Short-term/acute toxicity vs. long-term/cumulative toxicity
Inclusion of hepatotoxic backbones (e.g. DDI)
Non-nucleoside reverse transcriptase inhibitors (NNRTI): Nevirapine associated with hepatotoxicity, fibrosis &
clinical liver outcomes No association between efavirenz and liver outcomes
Protease inhibitors (PI): Liver steatosis Lower risks of fibrosis & cirrhosis, slower fibrosis
progression rates Comparison group: treatment naïve or mono/dual-therapy with
NRTI4
Research objective Estimating the rate of change in a marker
of liver fibrosis among new users of two classes of anchor agents for cART
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Methods
Canadian Co-infection Cohort Study
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New user design
CCC participants
N=1321
Unmatched sampleN=348
Matched sampleN=314
N=628 including repeats
- No chronic HCV infection (n=216)
- Not on 1st anchor class (n=334)
- On HCV treatment (n=23)
- Not on PI or NNRTI (n=192)
- Not on recommended backbone (n=177)
- Not on 1st line anchor agent (n=21)
- Hepatitis B infection (n=8)
- Unmatched NNRTI users (n=9)- Unmatched PI users (n=25)
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Liver fibrosis APRI score
Aspartate aminotransferase to platelet ratio
Validated in co-infected populations Accuracy comparable to other markers
Continuous score Predicts overall five-year survival in HCV infected
persons (HR: 2.8, 95% CI: 1.6, 4.7) Predicted by known predictors of liver disease
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Statistical analysis Rates of change in APRI score by class of
anchor agent and backbone Linear regression with generalized estimating
equations Outcome: Ln(APRI)
Covariates: Baseline: age, sex, time since HCV infection Time updated: alcohol use, CD4 count, HIV
viral load<50 copies/ml
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Results
Population characteristics
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Unmatched sample
Matched sample
PI NNRTI PI NNRTI
Number of participants
246 102 314 314
Alcohol use 131 (53) 63 (62) 167 (53) 172 (55)
Injection drug use 97 (39) 34 (33) 130 (41) 121 (38)
Undetectable HIV viral load
156 (63) 76 (74) 213 (68) 207 (66)
TDF/FTC backbone 155 (63) 73 (72) 211 (67) 218 (69)
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Median rates of change in APRI score per 5 years by regimen
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1.16 (1.04, 1.29)
1.03 (0.93, 1.12)
1.11 (1.02, 1.20)
1.08 (0.97, 1.19)
1.5 Significant liver fibrosis
PI + ABC/3TCPI + TDF/FTC
NNRTI + ABC/3TCNNRTI + TDF/FTC
Take home message 1st study restricted to modern cART regimens
Fibrosis development more influenced by backbone than class of anchor agent ABC/3TC associated with changes in APRI score
over time Study not designed to look at backbone specifically
Findings need to be confirmed WHO guideline for cART initiation (all populations):
EFV + TDF + (3TC or FTC)
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Acknowledgments The participants of HIV-HCV Canadian Cohort (CTN 222)
The Co-Investigators, Drs. Jeff Cohen, Brian Conway, Curtis Cooper, Pierre Côté, Joseph Cox, John Gill, David Haase, Shariq Haider, Marianne Harris, Mark Hull, Lynn Johnston, Valerie Martel-Laferriere, Julio Montaner, Erica Moodie, Neora Pick, Anita Rachlis, Danielle Rouleau, Aida Sadr, Stephen Sanche, Roger Sandre, Mark Tyndall, Marie-Louise Vachon, Sharon Walmsley, David Wong
We thank Brenda Beckthold, Claire Casavant, Isabelle Chabot, Warmond Chan, Jonathan Edwin, Elaine Fernandez, Claude Gagne, Marcela Gil, Heather Haldane, Judy Latendre-Paquette, Nancy McFarland, Jennifer Kocilowicz, Anja Mcneil, Mitra Motamedi, Renee Pugsley, Laura Puri for their assistance with study coordination, participant recruitment and care
The funding agencies: CIHR, FRSQ and CTN
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Thank you!
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