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Hepatitis C virus (HCV) coinfection is a strong risk factor for death of HIV-infected patients. Immune dysfunction affects the clinical course of acute hepatitis C (AHC). CD4/CD8 ratio is a biomarker of both persistent inflammation and immunosenescence in HIV-infected adults on effective antiretroviral therapy. A low CD4/CD8 ratio predicts immunosenescence and is associated with increased morbidity and mortality in both HIV-infected adults and elderly HIV-uninfected adults. Additionally, immunosenescence is associated with unresponsiveness to vaccine and could affect the immune reaction to pathogens during their primary infection. We retrospectively evaluated 12 AHC patients to assess the association between CD4/CD8 ratio and liver damage in AHC. We used the Spearman rank correlation test to assess the correlation. We found that CD4/CD8 ratio and peak alanine aminotransferase level (peak ALT) were positively correlated (r = 0.8322, p = 0.0013). The CD4 counts did not correlate with peak ALT (r = 0.5245, p = 0.0839). CD8 + T cells expansion for AHC did not affect these results, because the CD4/CD8 ratio before the onset of AHC and peak ALT positively correlate (n = 11; r = 0.7909, p = 0.0055) and there was no significant difference between CD4/CD8 ratios before and after the onset of AHC (n = 11; p = 0.9766). Immunosenescence may be negatively associated with the cellular immune response to acute HCV infection. We suggest that clinicians consider using CD4/CD8 ratio as a marker of immunosenescence in their management of patients with HIV infection and other complications., (Copyright © 2019. Published by Elsevier Ltd.)

A model for drug interaction between amlodipine and simvastatin was developed using concentration data obtained from a multiple-dose study consisting of single- and co-administration of amlodipine and simvastatin conducted in healthy Koreans. Amlodipine concentrations were assumed to influence the clearance of simvastatin and simvastatin acid, which as well as the oral bioavailability was allowed to vary depending on genetic polymorphisms of metabolic enzymes. Covariate effects on drug concentrations were also considered. The developed model yielded a 46% increase in simvastatin bioavailability and a 13% decrease in simvastatin clearance when amlodipine 10 mg was co-administered. When CYP3A4/5 polymorphisms were assessed by a mixture model, extensive metabolizers yielded a decrease in simvastatin bioavailability of 81% and a decrease in simvastatin clearance by 4.6 times as compared to poor metabolizers. Sixty percent of the usual dose was the optimal simvastatin dose that can minimize the interaction with amlodipine 10 mg. Age and weight had significant effects on amlodipine concentrations. In conclusion, this study has quantitatively described the pharmacokinetic interaction between simvastatin and amlodipine using a modeling approach. Given that the two drugs are often prescribed together, the developed model is expected to contribute to more efficient and safer drug treatment when they are co-administered.