Pharmacodynamics Of Antiretroviral Medicines Used For HAART In Chinese HIV Patients

BackgroundHighly active antiretroviral therapy is considered to be the only effective therapy of HIV/AIDS. Pharmocokinetics is different from person to person. In order to improve outcomes, reduce toxicity, and increase efficacy, therapeutic drug monitoring is used to adjust the individual dose. However, we don’t have the data of effective drug plasma concentration in Chinese population.ObjectiveTo evaluate the relationship between NVP/AZT/d4T concentrations and viralogical response, drug resistance and adiverse events in Chinese population.Materials and Methods244outpatients (male123, femal121) of HIV/AIDS clinic were enrolled randomly, all of whom were treated with HAART (NVP/AZT/d4T) and follow-up regularly. Blood samples were taken before administration, or2to4hours thereafter. Drug concentreation were detected by HPLC. Clinical informations and lab data were collected at the same time. The relationships between the concentration and clinic outcomes were analyzed.Results1. NVP-Ctrough (Trough concentration of NVP) in viralogical failure group (3.81μg/ml) or resistant group (3.23μg/ml) was lower than viralogical response group (5.40μg/ml, P=0.018).2.3.9μg/ml was a better low limit of NVP-Ctrough in Chinese population. The risk of viralogical failure and NVP resistance increased5.4times and6.3times when NVP-Ctrough was below3.9μg/ml.3. NVP-Ctrough in the severe hepatotoxicity group (8.20μg/ml) was higher than control group and mild hepatotoxicity group (5.48μg/ml, P=0.015) in male. The risk of severe hepatotoxicity increased2.4times when NVP-Ctrough is above8μg/ml. 4. NVP-Ctrough and Cpeak showed no correlation with rash.5. Peak concentration of AZT (AZT-Cpeak) in the hematotoxicity group (0.68μg/ml) was higher than the control group (0.25μg/ml, P=0.001).6. d4T Cpeak showed no correlation with hyperlipidemia, peripheral neuropathy or lipodystrophy.Conclusions1. NVP Ctrough showed significant correlation with viralogical response and resistant. Reduction of NVP Ctrough showed significant correlation with efficacy and resistant mutation.2. Elevation of NVP Ctrough showed significant correlation with severe hepatotoxicity, especially in male.3.3.9-8.0μg/ml were an appropriate effective drug plasma concentration in Chinese population.4. AZT Cpeak showed significant correlation with hematotoxicity.5. d4T Cpeak showed no correlation with hyperlipidemia, peripheral neuropathy or lipodystrophy.