Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin

• Proportion of patients with expected Cmax of rifampin. [ Time Frame: Weeks 1 and 10-12: rifampin time points at hours 0, 2, 4, 6 and 8. ] [ Designated as safety issue: No ]
  Expected maximum concentration of rifampin is 8-24 mcg/mL
  
  
• Proportion of patients with expected pre dose concentration of lopinavir. [ Time Frame: Weeks 2 and 10-12: lopinavir time points at hours 0, 2, 4, 6 and 8. ] [ Designated as safety issue: Yes ]
  The expected pre dose concentration of lopinavir is >1.0 mcg/mL.
  
  

• Proportion of patients with successful treatment of HIV therapy. [ Time Frame: 10-12 weeks ] [ Designated as safety issue: Yes ]
  HIV failure will be defined as failure to drop the viral load by 0.5 log 10 copies/mL drop by week 4 of treatment and a viral load drop >1 log 10 copies/ml by week 8.
  
  
• Proportion of patients with expected AUC of rifampin [ Time Frame: 10-12 weeks ] [ Designated as safety issue: No ]
  The expected AUC of rifampin is 44-70 mcg•h/mL
  
  
• Proportion of patient with success of tuberculosis therapy [ Time Frame: 10-12 weeks ] [ Designated as safety issue: No ]
  Success of treatment using criteria established by the Brazilian National Ttuberculosis Program.
  
  
• Proportion of patients with expected Cmax and AUC of lopinavir [ Time Frame: 10-12 weeks ] [ Designated as safety issue: No ]
  The expected Cmax of lopinavir is 6-14 mcg/mL. The expected AUC lopinavir is 56-130 µg•h/mL
  
  

This will be an open label non-randomized pharmacokinetic study of 10-12 HIV-infected patients co-infected with Mycobacterium tuberculosis.

Enrollment: Potential subjects with active tuberculosis who have tolerated a rifampin containing regimen for at least 2 weeks. Potential subjects will be referred from the surrounding communities to Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)

Visit 1: After enrollment the subject will have a baseline rifampin PK will be done. They will then be started on lopinavir/ritonavir containing HAART regimen with standard twice daily dosing. Ritonavir 100 mg capsules will be added to the regimen and the dose escalated until the patient is taking 3 capsules twice daily. The time between enrollment and visit 1 will be determined by the treating physician

Visit 2: They will return about 1 week after dose escalation has been completed to sample lopinavir concentrations.

Visit 3: Subject will return in 2 weeks to have repeat to review results of lopinavir concentrations and response to therapy. Ritonavir will be adjusted as needed.

Visit 4: Subject will then return in 4 weeks for last visit for evaluation. Lopinavir and rifampin PK will be done.