EFFECT OF NONNUCLEOSIDES (NNRTIs) ON TROUGH PLASMA LEVELS OF CONCOMITANT SAQUINAVIR-SGC (SQV) AND LOPINAVIR/RITONAVIR (LPV/RTV)

M Harris, C Alexander, L Ting, J Mostyn, S Guillemi, PR Harrigan, MV O’Shaughnessy, JSG Montaner
BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia

Background: Nevirapine (NVP) and efavirenz (EFV) decrease plasma levels of LPV. Increased LPV/ RTV doses are recommended to overcome this interaction. RTV boosting may also overcome the effect of these NNRTIs on SQV plasma levels. We examined the effect of NVP or EFV on trough PI levels in regimens including LPV/RTV and SQV-SGC.
Methods: HIV+ adults with prior failure of regimens including all 3 drug classes were prescribed nucleosides, LPV/RTV 400 mg/100 mg twice daily (533/133 mg if also taking NVP or EFV) and SQV-SGC 800 mg twice daily. A subgroup also received NVP 200 mg twice daily or EFV 300 mg twice daily. After a minimum of 2 weeks on a stable regimen, blood was drawn immediately before and every 2 hours for 12 hours after a timed, observed medication dose. Plasma was separated within 1 hour and stored at –70°C until analysis. Plasma drug concentrations were determined by a validated assay using HPLC coupled with tandem mass spectrometry. Lower limits of quantitation (LLQ) were 277 ng/mL for LPV, 46 ng/mL for SQV, 92 ng/mL for RTV, 136 ng/mL for NVP, and 300 ng/mL for EFV.
Results: The median trough LPV level was 3200 ng/mL (range: below LLQ-9030) among patients taking EFV or NVP (n=7) and 3845 (range: below LLQ-7015) among patients taking no NNRTI (n=5). The median trough SQV level was 550 ng/mL (range: below LLQ-2320) among patients taking EFV or NVP, and 240 (range: below LLQ-915) among patients taking no NNRTIs.
Conclusions: In our preliminary results, similar trough LPV levels are seen in patients taking NVP or EFV and those not taking an NNRTI, indicating that the increased LPV/RTV dose compensates for the effect of the NNRTI. The increased dose of RTV also compensates for the effect of NVP or EFV on SQV trough levels.