Pharmacological Interaction of Lopinavir/Ritonavir 800/200 mg BID and Rifampicin in Subjects Presenting Tuberculosis with Contraindication for an Efavirenz containing Antiretroviral Regimen

  • Stanis Schmaltz C
  • Martins Costa M
  • Cattani V
  • et al.
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Abstract

Rifampicin reduces plasma concentration of most HIV protease inhibitors. Lopinavir boosted with ritonavir (LPV/r) could be an option to treat TB-HIV patients. Our aim was to evaluate lopinavir interaction with rifampicin during TB-HIV therapy. TB-HIV patients who could not use efavirenz and with no genotypic resistance to lopinavir were included. Rifampicin 600 mg, isoniazid 400 mg and pyrazinamide 2000 mg were started at day one for 6 months and LPV/r plus two nucleoside/nucleotide reverse transcriptase inhibitors were introduced at day 30. LPV/r dose was started at 400/100 mg BID and escalated over 7 days to 800/200 mg BID. Pharmacokinetic sampling was performed at day 15 (rifampicin), 45, 90, 180 (rifampicin, lopinavir, ritonavir) and 210 (lopinavir, ritonavir). Viral load (VL) and CD4 counts were performed at baseline and days 30, 60, 120, and 180. Genotypic testing was done in baseline and in the last visit. Fifteen patients were enrolled. Five were excluded during exclusively TB therapy. After LPV/r introduction five patients were excluded, three due to adverse events, and two due to low adherence. Five patients finished the study, two of them with VL <50 copies/mL. LPV/r genotypic resistance was detected in one patient. Lopinavir concentrations were below 1 micro g/mL in 4/10 patients (in one study point), and one in two study points. Lopinavir concentrations were above 4 micro g/mL in 6/10 patients, at least in one pharmacokinetic sample. Although target drug concentrations of lopinavir were achieved for most patients, adverse events were frequent and low adherence was observed for both TB and HIV therapies, showing how difficult it is to treat both diseases simultaneously. Hepatic and pancreatic enzymes should be routinely monitored.

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Stanis Schmaltz, C. A., Martins Costa, M. J., Cattani, V. B., Pereira Pinto, D., Liporage, J., Benjamin, A., … Rolla, V. (2014). Pharmacological Interaction of Lopinavir/Ritonavir 800/200 mg BID and Rifampicin in Subjects Presenting Tuberculosis with Contraindication for an Efavirenz containing Antiretroviral Regimen. Journal of AIDS & Clinical Research. https://doi.org/10.4172/2155-6113.1000358

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