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AIDS:
doi: 10.1097/QAD.0b013e3283455e4b
Epidemiology and Social

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)

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Abstract

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.

© 2011 Lippincott Williams & Wilkins, Inc.

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