USE OF DELAVIRDINE (DLV) AND LOPINAVIR/r (LPV) IN HEAVILY PRE-TREATED PATIENTS

Michelle Jones, Salima Jutha, Jennie Prasad, Brian Conway
Department of Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia

Objectives: The design of antiretroviral regimens for heavily pre-treated patients (salvage therapy) is often hampered by the limited, complex options that remain available to us. Given the positive pharmacokinetic interactions that have been reported between DLV and LPV and the potential potency of this combination, we hypothesize that, adding a nucleoside analogue (NRTI), a simple three-drug regimen could be evaluated in salvage therapy. We have done so within the context of a prospective, observational study.
Methods: Patients attending a tertiary care referral clinic and who have experienced a virologic breakthrough while receiving at least one agent from each class were eligible. All patients received DLV 600 mg bid, LPV 2 capsules bid (reduced dose based on reported pharmacokinetic interactions) and NRTI(s). Follow-up clinical, virologic and immunologic evaluations were completed at weeks 2, 4, 8 and 12, then every three months, more frequently as appropriate.
Results: To date, 7 patients (all male) have been studied. All had prior exposure to at least 3 NRTIs, one NNRTI and one PI. In addition to DLV/LPV, patients received abacavir alone (4), or 3TC, d4T or d4T/3TC/abacavir (one each). Mean baseline CD4 count was 228 (10-450) cells/mm³, and plasma viral load 457,000 (17,000-750,000) copies/mL. In follow-up (mean 35 weeks), these values were 450 cells/mm³ and 3,990 copies/mL. Additional data on baseline and follow-up resistance testing and pharmacokinetic studies of DLV and LPV will be presented.
Conclusions: Simple (as few as 6 capsules bid, with 200 mg DLV capsules) salvage therapy regimens can be constructed, and appear to be effective in the medium term. The use of novel agents such as tenofovir and the refinement of this approach based on resistance and pharmacokinetic data may further enhance our ability to provide options for some of our most treatment-experienced patients.