title: Antiretroviral treatment interruption leads to progression of liver fibrosis in HIV-hepatitis C virus co-infection.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Divisions of Infectious Diseases/Immunodeficiency, Royal Victoria Hospital, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: Thorpe
authors.forename: Sahar
authors.initials: S
authors.lastname: Saeed
authors.forename: Erica E M
authors.initials: EE
authors.lastname: Moodie
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes; D002170:Canada; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008099:Liver / Q000276:immunology; D008103:Liver Cirrhosis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D044966:Anti-Retroviral Agents