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

University of Miami

Status and phase

Terminated

Phase 4

Conditions

AIDS

Tuberculosis

Treatments

Drug: Lopinavir/ritonavir and ritonavir

Study type

Interventional

Funder types

Other

Identifiers

NCT01700790

20100325

Details and patient eligibility

About

The object of this study is to evaluate the pharmacokinetic interactions, short term safety and efficacy of standard dose lopinavir/ritonavir 200mg/50 (two tablets twice daily) given with ritonavir 100 mg three tablets twice daily given in combination with rifampin in HIV-infected persons with tuberculosis

Full description

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: Subjects 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 and rifampin 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.

Enrollment

9 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Antiretroviral naive
If not antiretroviral naïve they must meet the following criteria:
- Taking Kaletra containing regimen with suppressed viral load.
- Taking an NNRTI or integrase containing regimen without prior history of use of PI for more than 2 weeks
- Taking an NNRTI or integrase containing regimen with prior exposure to PI greater than 2 weeks. It must be clearly stated in the source document that PI was switched to another agent for convenience.
- Taking another PI containing regimens with suppressed viral load. It must be clearly stated in source document that if another PI was used for greater than 2 weeks the regimen was switched to another agent for convenience. Subjects with prior history of PI use may be enrolled, if there is a genotype showing no resistance to Kaletra Other Inclusion criteria
Be at least 18 years of age and able to give informed consent.
Diagnosed with TB by criteria per Brazilian Ministry of Health
Have a good clinical response to TB.
Tolerating tuberculosis therapy containing rifampin for the 2 weeks prior to screening,except for persons taking protease inhibitors at time of diagnosis of TB.,. Subjects taking protease inhibitors will be screened and initiate visit 1 within 3 days of starting TB medication
HIV positive with documentation present in source document.
Have a CD4 cell count greater than 50 cells/mm3if not taking ART. Persons with cd4 < 50 may be enrolled, if it is felt that in the best interest of the patient, that enrollment in the study will allow for quicker initiation of antiretroviral therapy than referral to another treatment center.

Exclusion Criteria:

Non-compliance with DOTPlus. Alternatively DOT can be done by telephoning patient on a daily basis 5 times a week and having patient annotate taking drug in a log which would be reviewed by clinic staff
History of being treated for tuberculosis in the prior 2 years unless there is DST, including PCR testing, showing sensitivity to rifamycin.
Known hypersensitivity to rifampin or rifabutin.
Liver enzymes greater than 2 times ULN.
Bilirubin greater than 2 times ULN.
Serum creatinine greater than 3 times ULN.
Hemoglobin less than 7.0 gms even if receiving erythropoietin.
Absolute neutrophil count less than 750 cells/mm3 even if receiving G-CSF.
Fasting triglycerides greater than 400 mg/dL.
Fasting cholesterol > 1.6 upper limits of normal.
GI intolerance of tuberculosis medications requiring discontinuation of tuberculosis medications.
Fasting glucose greater 150 mg/dL.
Pregnant women.
Use of one of the prohibited medications
Any condition that the investigators feel could compromise the use of the current medication.
Have a CD4 cell count of 50 cells/mm3or less
Hepatitis B or C infection
Alcohol or illicit drug use, which in the investigators opinion may affect participation in study.