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Antiretroviral treatment interruption leads to progression of liver fibrosis in HIV–hepatitis C virus co-infection

Thorpe, Juliaa; Saeed, Sahara; Moodie, Erica EMb; Klein, Marina Ba; for the Canadian Co-infection Cohort Study (CTN222)

doi: 10.1097/QAD.0b013e3283455e4b
Epidemiology and Social

Objective: Despite potential negative consequences, HIV/hepatitis C virus (HCV) co-infected patients may discontinue antiretroviral treatment (ART) for several reasons. We examined the impact of ART interruption on liver fibrosis progression in co-infected adults, using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate marker of liver fibrosis.

Method: Data were analyzed from a multisite prospective cohort of 541 HIV–HCV co-infected adults. ART interruption was included as a time-updated variable and defined as the cessation of all antiretrovirals for at least 14 days. The primary endpoint was the development of an APRI score at least 1.5. Time-dependent Cox proportional hazards regression and inverse probability-of-treatment weighting (IPTW) in a marginal structural model were used to evaluate the association of baseline and time-varying covariates with developing significant fibrosis.

Results: Patients were followed for a median of 1.02 years; 10% (n = 53) interrupted ART and 10% (n = 53) developed significant fibrosis. After accounting for potential confounders, including CD4+ T-cell count, HIV viral load, baseline APRI score, age and gender, the hazard ratio for ART interruption was 2.52 (95% confidence interval 1.20–5.28). Use of IPTW resulted in a similar effect estimate, suggesting that mediation by time-varying confounders was negligible.

Conclusion: ART interruption was associated with an increased risk of fibrosis progression in HIV–HCV co-infection that was only partially accounted for by HIV viral load and CD4+ T-cell counts. Our findings suggest that liver disease progression observed in ART-treated co-infected patients is partly due to the consequences of treatment interruptions.

aDepartment of Medicine, Divisions of Infectious Diseases/Immunodeficiency, Royal Victoria Hospital, Canada

bDepartment of Epidemiology & Biostatistics, McGill University, Montreal, Quebec, Canada.

*Investigators are also the co-authors and listed in the Acknowledgments section.

Received 29 October, 2010

Revised 25 January, 2011

Accepted 3 February, 2011

Correspondence to Dr Marina B. Klein, Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Immunodeficiency Service, Montreal Chest Institute, 3650 Saint Urbain, Montreal, QC H2X 2P4, Canada. Tel: +1 514 934 1934 x32306; fax: +1 514 843 2092; e-mail:

© 2011 Lippincott Williams & Wilkins, Inc.