13th Annual Conference of the British HIV Association 29 March–1 April 2007, Brighton, UK

PHARMACOKINETICS OF A LOPINAVIR/r (LPV/r) CAPSULE TO TABLET SWITCH WHEN CO-ADMINISTERED WITH NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTI), NEVIRAPINE (NVP) AND EFAVIRENZ (EFV) AS PART OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)

HIV Med 2007; 8(Suppl. 1):13 (abstract no. P12)

David Ladenheim, Chinyere Okoli, Rajesh Varma and Chloe Orkin
Barts and The London NHS Trust, London, UK

AIMS: To investigate the pharmacokinetic effects of switching from LVP/r capsule formulation to tablets using the SPC suggested dose when co-administered with NNRTIs in HIV-1-positive patients.

METHODS: Retrospective case note review. Patient characteristic, disease stage, treatment history, CDC stage, CD4 count, HIV-1 viral load (VL), concurrent medication and trough concentration (C_trough) from therapeutic drug monitoring (TDM) were recorded as part of routine clinical care using High Performance Liquid Chromatography (HPLC) with patients on LPV/r and NNRTI in an ethically diverse clinic cohort. Therapeutic drug monitoring (TDM) analysed in two treatment groups: 400 mg LPV/r (three capsules) bd with NNRTI (n=6) and 533 mg LPV/r (4 capsules) bd with NNRTI (n=8). Serum samples for both groups were taken while on the capsule formulation of LVP/r. Repeat levels were requested after the switch to tablets at a dose of 600 mg/150 mg (three tablets) bd once patients had reached steady state (>2 weeks after switch).

RESULTS: 14 patients identified (12 male), one Asian, five Black African, eight Caucasian. Mean age 41 years. Median CD4 count 515 cells/mm³. All 14 patient had VL <50 copies/mL prior to switch. The dose increase to 600 mg/150 mg did not produce a uniform increase in C_trough of LVP/r for all patients. 4/7 EFV and 2/7 NVP patients had a lower C_trough lopinavir following switch to tablets. 4/7 patients had sub-therapeutic NVP levels while on LVP/r capsules, 3/4 remained subtherapeutic after switching. No patient had virological failure subsequent to switch or reported any adverse events.

DISCUSSION: Intra-patient variability may account for the unexpected reduction in Lop/r levels despite the increased dose. The unpredictability of Lop/r and NVP levels suggests a role for TDM of both classes. Larger studies are needed to evaluate the significance in treatment-experienced patients.

2007-03-29
P12

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