A longitudinal analysis of liver fibrosis progression among NNRTI and PI users in the Canadian co-infection cohort study

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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 2015
• 21 July 2015

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Background
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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 NRTI

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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
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Canadian Co-infection Cohort Study
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New user design

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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
  loadlt50 copies/ml

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Results
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Population characteristics
Unmatched sample Unmatched sample Matched 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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(No Transcript)
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Median rates of change in APRI score per 5 years
by regimen
1.5
Significant liver fibrosis
1.08 (0.97, 1.19)
1.03 (0.93, 1.12)
1.16 (1.04, 1.29)
1.11 (1.02, 1.20)
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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!

• Questions?