THE EFFECT OF HAART ON LIVER DISEASE PROGRESSION IN HIV INFECTION
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Background: Liver disease, primarily due to viral hepatitis coinfection, is a leading cause of death among HIV-infected individuals. The purpose of this research was to determine the influence of highly active antiretroviral therapy (HAART) on liver disease progression using the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), a non-invasive surrogate for hepatic fibrosis. Methods: First, we performed a cross-sectional study to assess the risk for hepatic fibrosis as measured by APRI among 4 groups of participants in the Multicenter AIDS Cohort Study (MACS): (1) HIV- and viral hepatitis-uninfected; (2) HAART-naive HIV-monoinfected; (3) viral hepatitis-monoinfected; (4)HAART-naïve HIV-viral hepatitis coinfected. Next, among the HIV-infected participants who initiated HAART during follow-up, we conducted a prospective study of APRI change before and after HAART initiation. Finally, we performed a nested case-control study to evaluate the association of changes in APRI with liver-related mortality within our cohort. Results: Prior to HAART initiation, the median APRI was highest in the HIV-viral hepatitis-coinfected men (1.0) followed by the viral hepatitis-monoinfected (0.43), HIV-monoinfected (0.42), and uninfected men (0.27). HIV, viral hepatitis, and the interaction between HIV and viral hepatitis infections were independently associated with higher APRI. Among the HIV-infected men, high HIV RNA and low CD4 counts were independently associated with an elevated APRI. Among HAART initiatiors, APRI increased across the interval 4-years to 1-year before HAART in both the HIV-viral hepatitis-coinfected and HIV-monoinfected men (34% and 17% increase, respectively). However, APRI decreased after HAART for both groups, particularly in the early post-HAART period and in those achieving an undetectable HIV RNA. Finally, among 57 men with viral hepatitis (91% with HIV) who died of liver disease, APRI was consistently higher as compared to matched controls for up to 9 years before death. APRI also rapidly increased in the 3 years prior to death among cases but remained stable among controls. Conclusions: Untreated HIV infection increases the risk of hepatic fibrosis, even in the absence of viral hepatitis infection. Although the biologic basis for liver disease in the setting of HIV is unclear, ongoing HIV replication is likely an important mediator, and effective HAART mitigates liver disease progression.