AIDS | Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin
AIDS research study
What is the primary objective of this study?
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
Who is eligible to participate?
- 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.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Lopinavir/ritonavir and ritonavirTwo tablets twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 capsules of ritonavir 100 mg twice daily given with rifampin 600 mg daily
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Lopinavir/ritonavir and ritonavirTwo tablets of twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 tablets of ritonavir 100 mg of twice daily given with rifampin 600 mg daily.
Start Date: February 2016
Completed Date: December 31, 2018
Phase: Phase 4
Primary Outcome: Proportion of patients with expected pre dose concentration of lopinavir.
Secondary Outcome: Proportion of patients with successful treatment of HIV therapy.
Study sponsors, principal investigator, and references
Principal Investigator: Catherine Boulanger, MD.
Lead Sponsor: University of Miami
Collaborator: Oswaldo Cruz Foundation
Ren Y, Nuttall JJ, Egbers C, Eley BS, Meyers TM, Smith PJ, Maartens G, McIlleron HM. Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis. J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):566-9. doi: 10.1097/QAI.0b013e3181642257.