title: The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy.
abstract: OBJECTIVE
  Rifampicin co-administration dramatically reduces plasma lopinavir concentrations. Studies in healthy volunteers and HIV-infected patients showed that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional ritonavir offsets this interaction. However, high rates of hepatotoxicity were observed in healthy volunteers. We evaluated the safety, effectiveness and pre-dose concentrations of adjusted doses of LPV/r in HIV infected adults treated with rifampicin-based tuberculosis treatment.
  
  
  METHODS
  Adult patients on a LPV/r-based antiretroviral regimen and rifampicin-based tuberculosis therapy were enrolled. Doubled doses of LPV/r or an additional 300 mg of ritonavir were used to overcome the inducing effect of rifampicin. Steady-state lopinavir pre-dose concentrations were evaluated every second month.
  
  
  RESULTS
  18 patients were enrolled with a total of 79 patient months of observation. 11/18 patients were followed up until tuberculosis treatment completion. During tuberculosis treatment, the median (IQR) pre-dose lopinavir concentration was 6.8 (1.1-9.2) mg/L and 36/47 (77%) were above the recommended trough concentration of 1 mg/L. Treatment was generally well tolerated with no grade 3 or 4 toxicity: 8 patients developed grade 1 or 2 transaminase elevation, 1 patient defaulted additional ritonavir due to nausea and 1 patient developed diarrhea requiring dose reduction. Viral loads after tuberculosis treatment were available for 11 patients and 10 were undetectable.
  
  
  CONCLUSIONS
  Once established on treatment, adjusted doses of LPV/r co-administered with rifampicin-based tuberculosis treatment were tolerated and LPV pre-dose concentrations were adequate.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Decloedt
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
authors.forename: Concepta
authors.initials: C
authors.lastname: Merry
authors.forename: Funeka
authors.initials: F
authors.lastname: Bango
authors.forename: Helen
authors.initials: H
authors.lastname: McIlleron
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D061466:Lopinavir; D019438:Ritonavir; D012293:Rifampin