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!

Questions?