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

Department of Medicine, Divisions of Infectious Diseases/Immunodeficiency, Royal Victoria Hospital, Canada.
AIDS (London, England) (Impact Factor: 6.56). 02/2011; 25(7):967-75. DOI: 10.1097/QAD.0b013e3283455e4b
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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