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3rd International AIDS Society Conference on HIV Pathogenesis and TreatmentRio de Janeiro - July 24 - 27, 2005 |
INTRACELLULAR CONCENTRATIONS OF 3TC-TRIPHOSPHATE, CARBOVIR-TRIPHOSPHATE AND TENOFOVIR-DIPHOSPHATE REMAIN STABLE THROUGHOUT 36 WEEKS OF NRTI TREATMENT INTERRUPTED BY NRTI FREE TREATMENT PERIODS IN PATIENTS WITH MULTIRESISTANT HIV
IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. WePe3.2C04
Stocker H.1, Kruse G.2, Weber C.1, Breske A.2, Kreckel P.1, Walter H.3, Sopper S.4, Kurowski M.2, Arastéh K.1
1 Vivantes Auguste-Viktoria Klinikum, KompNet HIV/AIDS, Berlin, Germany, 2 HIV-Lab c/o Vivantes Auguste-Viktoria Klinikum, KompNet HIV/AIDS, Berlin, Germany, 3 Universität Erlangen, KompNet HIV/AIDS, Erlangen, Germany, 4 Deutsches Primatenzentrum, KompNet HIV/AIDS, Göttingen, Germany
INTRODUCTION: Little is known about intracellular concentrations of phosphorylated NRTI in the course of NRTI treatment. Induction or downregulation of cellular kinases may influence the NRTI phosphorylation process. Changes in the expression of membrane bound drug transporters may also influence the concentration of the active drugs. The objective of this sub-study was to identify changes in intracellular concentrations of NRTI-tri/diphosphates during treatment with 3TC, ABC and TDF.
METHODS: 10 patients with multiresistant HIV were included in a study which was designed to investigate the virological, immunological and pharmacological effects of a treatment strategy which involves repeated switches between NRTI-only and PI-only containing regimens. We present here the results of the pharmacological sub-study. Samples for the determination of intracellular drug concentrations were taken in intervals of 2 to 4 weeks. PBMC were isolated from blood which had been collected 10h to 14h after 3TC and ABC administration and 22h to 26h after TDF administration. Intracellular tri/diphosphate concentrations were measured using LC-MS/MS.
RESULTS: Each patient had at least two NRTI treatment cycles separated by a PI treatment cycle. The mean duration of the NRTI cycles and PI cycles were 97 and 47 days respectively. The geometric mean Ctrough [fmol/MIO cells] (95% CI) of 3TC-TP, CBV-TP (phosphorylated form of ABC) and TDF-DP were 7580 (n=40; 6140 - 9360), 290 (n=28; 231 - 364), 226 (n=25; 177 - 290) respectively. The intracellular concentrations two weeks and 36 weeks after baseline were not significantly different. Within each individual, inter and intra cycle variability of phosphorylated drug concentrations was low. There was no correlation between the intracellular drug level and virus load.
CONCLUSIONS: Intracellular concentrations of phosphorylated NRTI remain stable throughout prolonged NRTI treatment. After intercurrent interruptions of NRTI treatment concentrations promptly return to pre-interruption values. In patients with multiresistant HIV the intracellular drug levels do not have a significant impact on virus load.
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050724
Clinical | WePe3.2C04 | Hartmut Stocker
Pharmacological monitoring of ARV therapy
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