TY - JOUR
T1 - Drug monitoring of antiretroviral therapy for HIV-I infection
T2 - Method validation and results of a pilot study
AU - Moyer, Thomas P.
AU - Temesgen, Zelalem
AU - Enger, Robert
AU - Estes, Lynn
AU - Charlson, Joel
AU - Oliver, Lawrence
AU - Wright, Alan
PY - 1999
Y1 - 1999
N2 - Background: Antiretroviral therapy for HIV-1 infection has become increasingly complex. The availability of new and potent drugs and progress in understanding the pathogenesis of HIV-1 infection have led to the establishment of new treatment paradigms. The varying dosing regimens, associated toxicities, and the potential for drug-drug and food-drug interactions further complicate treatment. This complexity contributes to patient nonadherence. Because clinicians have no tools to monitor adherence or drug-drug interactions and because response requires that therapy exceed the known inhibiting concentration, 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, precision 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 concentrations of delavirdine, lamivudine, nevirapine, indinavir, nelfinavir, ritonavir, and saquinavir and peak serum concentrations of stavudine, zidovudine, and didanosine with reasonable precision. Results: Peak indinavir serum concentrations in most patients were in the range of 1-10 mg/L, and trough concentrations were in the range of 0.1-0.5 mg/L. Peak stavudine concentrations were in the range of 0.3-1.3 mg/L, and trough concentrations were in the range of 0.1-0.5 mg/L. Peak zidovudine concentrations were in the range of 0.1-1.1 mg/L. Conclusions: Because this was a blood serum concentration-seeking pilot study 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 from studies of monotherapy.
AB - Background: Antiretroviral therapy for HIV-1 infection has become increasingly complex. The availability of new and potent drugs and progress in understanding the pathogenesis of HIV-1 infection have led to the establishment of new treatment paradigms. The varying dosing regimens, associated toxicities, and the potential for drug-drug and food-drug interactions further complicate treatment. This complexity contributes to patient nonadherence. Because clinicians have no tools to monitor adherence or drug-drug interactions and because response requires that therapy exceed the known inhibiting concentration, 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, precision 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 concentrations of delavirdine, lamivudine, nevirapine, indinavir, nelfinavir, ritonavir, and saquinavir and peak serum concentrations of stavudine, zidovudine, and didanosine with reasonable precision. Results: Peak indinavir serum concentrations in most patients were in the range of 1-10 mg/L, and trough concentrations were in the range of 0.1-0.5 mg/L. Peak stavudine concentrations were in the range of 0.3-1.3 mg/L, and trough concentrations were in the range of 0.1-0.5 mg/L. Peak zidovudine concentrations were in the range of 0.1-1.1 mg/L. Conclusions: Because this was a blood serum concentration-seeking pilot study 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 from studies of monotherapy.
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U2 - 10.1093/clinchem/45.9.1465
DO - 10.1093/clinchem/45.9.1465
M3 - Article
C2 - 10471649
AN - SCOPUS:0032870854
SN - 0009-9147
VL - 45
SP - 1465
EP - 1476
JO - Clinical chemistry
JF - Clinical chemistry
IS - 9
ER -