LAUSR

BACKGROUND Rifampin induces the metabolism of many medications. To overcome the reduction in serum concentrations of lopinavir/ritonavir (LPV/r) when used with rifampin, 800/200 mg or 400/400 mg doses are used. OBJECTIVES To evaluate the super-boosted LPV/r (400/400mg) combination in HIV-TB patients for adequate concentrations, short term safety and tolerability, and short term clinical response to HIV and TB therapy. METHODS This was an open label, non-randomized pharmacokinetic (PK) study in HIV-TB patients. The primary objective was to determine the PK profile of LPV/r (400/400 mg) when given with rifampin-based TB regimen. The secondary objectives were short term safety, tolerability, and clinical response. The primary endpoints were a lopinavir trough value of >1.0 mcg/mL and rifampin maximum concentration (Cmax) of 8-24 mcg/mL. The secondary PK endpoints were rifampin area under the concentration-time curve from time zero to 24 hours (AUC0-24) of 44-70 mcg•h/mL, lopinavir Cmax of 6-14 mcg/mL, and lopinavir AUC0-12 56-130 mcg•h/mL. RESULTS Eleven patients were enrolled (10 male), ages 29-43 years. Two patients were discontinued due to non-compliance. Lopinavir trough of >1.0 mcg/mL was met in a least one of the PK samplings on all 9 subjects who completed treatment. All patients met lopinavir Cmax and AUC0-12 targets. Five patients achieved the primary endpoint of rifampin Cmax (≥8 mcg/mL) in at least one of the PK sampling visits and 5 achieved the minimum AUC (≥44 mcg•h/mL). One grade 3 adverse event reported. CONCLUSIONS Super boosted LPV/r was safe and effective in HIV-TB patients. ClinicalTrials.gov Identifier NCT01700790.