Abstract
The effects of highly active antiretroviral therapy (HAART) on progression of hepatic fibrosis in HIV-hepatitis C virus (HCV) co-infection are not well understood. Deaths from liver diseases have risen in the post-HAART era, yet some cross-sectional studies have suggested that HAART use is associated with improved fibrosis rates. In a retrospective cohort of 533 HIV mono-infected and 127 HIV/HCV co-infected patients, followed between January 1991 and July 2005 at a university-based HIV clinic, we investigated the relationship between cumulative HAART exposure and hepatic fibrosis, as measured by the aspartate aminotransferase-to-platelet ratio index (APRI). We used a novel methodological approach to estimate the dose-response relationship of the effect of HAART exposure on APRI. HAART was associated with increasing APRI over time in HIV/HCV co-infected patients suggesting that they may be experiencing cumulative hepatotoxicity from antiretrovirals. The estimated median change (95% confidence interval) in APRI per one year of HAART intake was of −0.46% (−1.61% to 0.71%) in HIV mono-infected compared to 2.54% (−1.77% to 7.03%) in HIV/HCV co-infected patients. Similar results were found when the direct effect of HAART intake since the last visit was estimated on the change in APRI. HAART use associated is with increased APRI in patients with HIV/HCV co-infection. Therefore treatment for HCV infection may be required to slow the growing epidemic of end-stage liver disease in this population.
Highlights
We further evaluated the effect of highly active antiretroviral therapy (HAART) on liver disease progression and found that cumulative exposure, to protease inhibitor-based regimens, was associated with increasing fibrosis in HIV/hepatitis C virus (HCV) co-infected patients and, to a lesser but significant extent, in patients infected with HIV only.[23]
We began by examining change in lnAPRI between clinic visits caused by the dose of HAART received in that time, that is, we examined the direct or ‘‘cross-sectional’’ effect of most recent HAART intake on the change in aminotransferase-to-platelet ratio index (APRI)
We used an extension of the propensity scores approach, the Generalized Propensity Score (GPS)[26,27,28] that has been broadened to the repeated measures data scenario (as described in Estimation of Dose-Response Functions for Longitudinal Data using The Generalized Propensity Score by EEM Moodie and DA Stephen (2009), manuscript in revision) to estimate the marginal dose-response curve to model the effect of HAART on liver function as measured by the lnAPRI
Summary
Since the advent of highly active antiretroviral therapy (HAART) there have been dramatic reductions of morbidity and mortality from virtually all causes among HIV-infected persons.[1,2] One of the glaring exceptions to this trend is liverrelated deaths which represent one of the leading causes of death among HIV-infected individuals.[3,4,5,6,7,8] Much of this excess mortality has been driven by the epidemic of Hepatitis C (HCV) co-infection affecting more than 30% of HIV-infected patients in developed countries.[9,10] HCV progresses more rapidly in patients co-infected with HIV.[11,12,13] In addition, non-alcoholic steato-hepatitis is increasingly being recognized as an important cause of liver disease in HIV-infected persons which may contribute to liver-related morbidity in the absence of HCV infection.[14]A number of cross-sectional studies have suggested that HAART, especially regimens containing protease inhibitors (PI) [15,16,17], is associated with improved fibrosis rates. Since the advent of highly active antiretroviral therapy (HAART) there have been dramatic reductions of morbidity and mortality from virtually all causes among HIV-infected persons.[1,2] One of the glaring exceptions to this trend is liverrelated deaths which represent one of the leading causes of death among HIV-infected individuals.[3,4,5,6,7,8] Much of this excess mortality has been driven by the epidemic of Hepatitis C (HCV) co-infection affecting more than 30% of HIV-infected patients in developed countries.[9,10] HCV progresses more rapidly in patients co-infected with HIV.[11,12,13] In addition, non-alcoholic steato-hepatitis is increasingly being recognized as an important cause of liver disease in HIV-infected persons which may contribute to liver-related morbidity in the absence of HCV infection.[14]. The net effect of HAART on liver disease remains unclear
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