POPULATION PHARMACOKINETICS OF ANTIRETROVIRAL DRUGS IN HCV/HIV OR HBV/HIV CO-INFECTED INDIVIDUALS

J.P. Cruz1,2, D. Matias1, C. Carvalho1, J. Morais2, E. Valadas3, F. Antunes3

1) Pharmacology and Pharmacogenetics Laboratorial Unit, Laboratório de Diagnóstico Molecular de Doenças Infecciosas, Faculdade de Medicina da Universidade de Lisboa; 2) iMed.UL – Research Institute for Medicines and Pharmaceutical Sciences; 3) Clinica Universitária de Doenças Infecciosas, Faculdade de Medicina da Universidade de Lisboa.

•The human immunodeficiency virus (HIV) infection affects more than 40 million individuals worldwide;

•About one quarter of every HIV-infected individual in developed world is also HCV infected and about one tenth HIV-infected individuals are HBV infected. These co-infections speed up liver disease progression and HIV immune system deterioration;

•Drug efficacy is dependent on the amount of drug available on site of action. Most antiretroviral drugs are mainly metabolized by liver enzymes. Consequently, the presence of liver disease can influence their efficacy. Pharmacokinetics of antiretroviral drugs in co-infected patients should then be assessed;

•This study was designed to compare ajusted bayesian pharmacokinetic parameters in co-infected patients versus non co-infected patients.

Introduction and purpose

Conclusions•This preliminary study reveals a small association between some adjusted bayesian pharmacokinetic parameters of antiretroviral drugs and the presence of HCV or HBV co-infection in HIV-infected patients. The lopinavir Cmin was significantly influenced by the presence of viral hepatitis, however the statistical association of the other adjusted lopinavir pharmacokinetic parameters was not so clear. •To disclose further association between the presence of HIV-HCV or HIV-HBV co-infection and antiretroviral pharmacokinetics, more robust data are needed.

Discussion•A clear association between hepatic enzymes (GPT, GOT, GGT) and co-infection was

found (p < 0,05). Also urea plasma levels showed correlation with the presence of viral hepatitis (t-test, p = 0,009) (results not shown).

•The statistical analysis showed a significant difference in lopinavir Cmin (MW-test, p < 0,05) with higher mean±SD Cmin values for co-infected patients (3953±679 ng/mL versus 2383±1389 ng/mL).

•The adjusted bayesian pharmacokinetic parameters obtained showed no statistically significant differences except for a trend in lopinavir half-life (t-test, p = 0,07).

Results

•60 HIV-infected patients on triple antiretroviral therapy from the Clinical Ward of Infectious Diseases of Santa Maria Hospital (Lisbon) were enrolled;

•Blood samples were collected between 8 and 24 hours post-dose (trough concentration / Cmin) and analyzed by an HPLC-UV validated method;

•Individual demographic and clinical data were retrieved;

•Aboottbase PKS software was used to estimate adjusted bayesian pharmacokinetic parameters (clearance, volume of distribution, elimination rate constant, half-life) and Cmin;

•All results were analyzed in IBM SPSS 17.0 by Mann-Whitney (MW-test) or t-Student tests (t-test) .

Methods

Figure 1 – Study drug distribuition.

Table 1 – Study population charateristics.

Table 2 – Adjusted bayesian pharmacokinetic parameters for non nucleoside reverse transcriptase inhibitors.

Table 3 – Adjusted bayesian pharmacokinetic parameters for protease inhibitors.