Drug monitoring of antiretroviral therapy for HIV-I infection: Method validation and results of a pilot study

Background: Antiretroviral therapy for HIV-1 infection has become increasin gly complex. The availability of new and potent drugs and progress in under standing the pathogenesis of HIV-1 infection have led to the establishment of new treatment paradigms. The varying dosing regimens, associated toxicit ies, and the potential for drug-drug and food-drug interactions further com plicate treatment. This complexity contributes to patient nonadherence. Bec ause clinicians have no tools to monitor adherence or drug-drug interaction s and because response requires that therapy exceed the known inhibiting co ncentration, serum monitoring of antiretroviral therapy may play a role in improving treatment of HIV-1 infection. We report methods to quantify serum concentrations of antiretroviral drugs used to treat HIV-1 infection, prec ision and interference studies of these methods, and results observed in a pilot evaluation of blood serum concentrations from 12 human subjects. Methods: HPLC offers adequate sensitivity to measure peak or trough serum c oncentrations of delavirdine, lamivudine, nevirapine, indinavir, nelfinavir , ritonavir, and saquinavir and peak serum concentrations of stavudine, zid ovudine, and didanosine with reasonable precision. Results: Peak indinavir serum concentrations in most patients were in the r ange of 1-10 mg/L, and trough concentrations were in the range of 0.1-0.5 m g/L. Peak stavudine concentrations were in the range of 0.3-1.3 mg/L, and t rough concentrations were in the range of 0.1-0.5 mg/L. Peak zidovudine con centrations were in the range of 0.1-1.1 mg/L. Conclusions: Because this was a blood serum concentration-seeking pilot stu dy to evaluate analytic performance, we do not report on the correlation of drug response to blood concentration. However, the concentrations observed in patients are generally consistent with blood concentrations reported fr om studies of monotherapy. (C) 1999 American Association for Clinical Chemi stry.