Immune Activation and Drug Absorption in HIV-Infected Patients
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01845298|
Recruitment Status : Completed
First Posted : May 3, 2013
Last Update Posted : March 3, 2017
|Condition or disease||Intervention/treatment||Phase|
|HIV Infection||Drug: Rifampicin 600 mg||Not Applicable|
The dosing scheme for rifampicin for the treatment of tuberculosis was developed in the pre-HIV era, and achieving target concentrations at the site of infection is important for a successful outcome. Rifampicin is the least well absorbed of the first-line anti-TB drugs and may depend on active transport across the intestinal barrier. Rifampicin malabsorption is frequently observed in HIV/tuberculosis patients, but cannot be predicted by patient factors such as CD4+ T cell count, viral load, or the presence of diarrhea. Most importantly, loss of rifampicin absorptive capacity in the setting of HIV infection would explain the inferior treatment outcomes that are characteristic of HIV-associated tuberculosis, including early mortality, relapse after the completion of therapy, and the development of rifampicin-resistant infection during anti-tuberculosis therapy.
The gut-associated lymphoid tissue is the site of early and dramatic lymphocyte depletion in HIV+ patients, with near complete loss of intestinal CCR5+ CD4+ T cells within the first few weeks of infection. Lymphocyte depletion is accompanied by the loss of intestinal epithelial barrier integrity, and recent attention has focused on potential role of bacterial translocation across the damaged ("leaky") intestinal barrier. In support of this model, systemic immune activation markers have been shown to predict HIV progression better than CD4+ T cell count or HIV viral load. Independent of the potential role of bacterial translocation, the damage to gut epithelium may have other profound consequences for the HIV-infected patient.
The impact of this disease progression on the enterocyte's capacity to absorb specific drugs and nutrients has not been adequately explored. Loss of rifampicin absorptive capacity in the setting of HIV infection would explain the inferior treatment outcomes that are characteristic of HIV-associated tuberculosis, including early mortality, relapse after the completion of therapy, and the development of rifampicin resistant infection during anti-tuberculosis therapy. Therefore, we propose a pilot study of the relationship between immune activation, rifampicin absorption, and intestinal capacity for carrier-mediated transport and permeability, which will lay the foundation for a K23 Career Development Award application to the Division of AIDS, NIAID.
Rifampicin is an-antibacterial compound from the rifamycin family that is used for the treatment of certain bacterial infections, and is the cornerstone of the first-line treatment regimen for tuberculosis. Polymorphisms in a specific drug uptake transporter gene, SLCO1B1, lead to significant variability in the pharmacokinetics of rifampicin. Other host factors that negatively influence rifampicin absorption are not well understood, particularly in the high-risk group of HIV-infected patients with active tuberculosis.
Long-term use of rifampicin is rarely associated with adverse effects that include a flu-like illness and anemia. Both of these effects cease after termination of the drug. Neither of these effects has been reported after a single dose administration. Hypersensitivity reactions presenting with rash have also been reported after prolonged use of rifampicin, but would be rare after a single-dose administration. The risks associated with rifampicin have been minimized by studying pharmacokinetics after administration of a single dose, rather than after prolonged use. Rifampicin is a potent inducer of the cytochrome p450 enzyme system that is involved in the metabolism of many commonly used therapeutic compounds. For this reason, we will exclude participants who are receiving any prescription medications with clinically significant drug-drug interactions with rifampicin.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Immune Activation and Drug Absorption in HIV-Infected Patients|
|Study Start Date :||June 2014|
|Actual Primary Completion Date :||March 2016|
|Actual Study Completion Date :||March 14, 2016|
Experimental: HIV-infected subjects
HIV-infected subjects who have not yet initiated highly active antiretroviral therapy (HAART). All enrolled subjects will receive a single dose of rifampicin 600 mg.
Drug: Rifampicin 600 mg
The investigators will administer a single dose of rifampicin 600 mg to study subjects in order to conduct a pharmacokinetic study of rifampicin absorption.
Other Name: rifamycin
- Rifampicin Absorption (Ka) [ Time Frame: Baseline ]The investigators will perform a pharmacokinetic study to assess rifampicin absorption among study subjects. Pharmacokinetic modeling will be used to assess the absorption rate constant (Ka) for each subject.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01845298
|United States, Pennsylvania|
|Drexel University College of Medicine|
|Philadelphia, Pennsylvania, United States, 19102|
|Principal Investigator:||Christopher Vinnard, MD||Faculty|