Effect of zidovudine therapy in patients with HIV infection on endogenous interferon plasma levels and the hepatic cytochrome P450 enzyme system.
In this study, we wanted to investigate if there are differences in endogenous interferon (IFN) plasma levels in patients with different stages of HIV infections before and after therapy with zidovudine (ZDV) and determined the influence of ZDV therapy on the hepatic monooxygenase system by measuring the antipyrine pharmacokinetics. Therefore we investigated the endogenous IFN plasma levels in patients with asymptomatic HIV infection (CDC/WHO A1, n = 10) and patients with AIDS (CDC/WHO C3, n = 10). In AIDS plasma IFN-alpha and IFN-gamma levels are elevated (15.6 +/- 5.8 U/ml; 2.1 +/- 0.7 U/ml) compared to patients with an asymptomatic HIV infection (6.1 +/- 3.3 U/ml; 0.6 +/- 0.3 U/ml). The antipyrine clearance was significantly reduced in the group of AIDS patients (43.1 +/- 7.2 ml/min compared to 56.4 +/- 8.7 ml/min). In a second study with 11 patients in stage CDC/WHO A1/2 and CDC/ WHO B/C3 each, we studied the effect of a 14-day administration of ZDV on the endogenous plasma IFN levels and the CYP450 enzyme activity using the antipyrine pharmacokinetics as a parameter. We investigated the antipyrine clearance, clearance to metabolite and half-life by using HPLC. IFNs were measured by RIA or ELISA, respectively. In the first group no significant alterations of antipyrine kinetics or plasma IFN levels were observed after treatment with ZDV. In contrast to these results, we found a significant decrease in IFN-alpha and IFN-gamma (19.8 +/- 3.6 U/ml, 4.6 +/- 1.5 U/ml before; 7.9 +/- 2.6 U/ml, 1.9 +/- 1.3 U/ml after administration of ZDV), a decrease in antipyrine half-life, an elevation of the antipyrine clearance (49.8 +/- 15.7 ml/min, 57.3 +/- 13.7 ml/min) and an elevation of the clearances to metabolite.