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

作者：Thorpe Julia; Saeed Sahar; Moodie Erica E M; Klein Marina B^*

来源：AIDS, 2011, 25(7): 967-975.

DOI：10.1097/QAD.0b013e3283455e4b

• antiretroviral treatment interruption
• co-infection
• hepatitis C virus
• HIV
• liver fibrosis

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.

• 出版日期2011-4-24