Pharmacokinetics of Emtricitabine/Tenofovir/Efavirenz in HIV-infected Patients With Tuberculosis

The Pharmacokinetics of Co-formulated Emtricitabine/Tenofovir/Efavirenz in HIV-infected Patients With Smear-positive Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania

In this pilot study the pharmacokinetics and safety of the antiretroviral combination of co-formulated emtricitabine/tenofovir/efavirenz will be studied in HIV-positive patients with pulmonary tuberculosis (TB) who are concomitantly treated with a standard rifampin-containing tuberculostatic regimen. It is expected that this antiretroviral combination causes minimal drug interactions with the rifampin-containing anti-tuberculosis medication.

The primary objectives of this pilot study in 30 patients are:

1. To determine the effect of rifampin-containing tuberculostatic treatment on the pharmacokinetic profile of emtricitabine+tenofovir+efavirenz, when co-formulated in one tablet, in HIV-infected patients with smear-positive pulmonary tuberculosis in Tanzania.
2. To determine the effect of the emtricitabine+tenofovir+efavirenz regimen on the pharmacokinetics of tuberculostatics in the same population.

The secondary objectives are:

1. To determine the safety of co-administration of emtricitabine+tenofovir+efavirenz with treatment for smear-positive pulmonary tuberculosis.
2. To determine the short-term (24 weeks) virological efficacy on HIV of an emtricitabine+tenofovir+efavirenz regimen in patients with smear-positive pulmonary tuberculosis.
3. To determine the short-term bacteriological efficacy on smear-positive tuberculosis of the co-administration of a standard regimen for tuberculosis and an emtricitabine+tenofovir+efavirenz regimen.

Inclusion Criteria:

• A smear-positive pulmonary tuberculosis, based on positive smear of at least two sputum samples with Ziehl-Neelsen (ZN) staining.
• HIV-infected as documented by positive HIV antibody test.
• Subject is at least 18 years of age at the day of the first dosing of study medication.
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• CD4 cell count > 50 copies/mm3.
• Karnofsky score > 40.
• Willing and able to regularly attend the Kibung'oto National Tuberculosis Hospital (KNTH) clinic.

Exclusion Criteria:

• History of sensitivity/idiosyncrasy to the drug or chemically related compounds or excipients, which may be employed in the trial.
• Previously treated for HIV infection with antiretroviral agents.
• Pregnant or breastfeeding.
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
• A history of severe psychiatric disease such as psychosis, schizophrenia, etc.
• Inability to understand the nature and extent of the trial and the procedures required.
• Abnormal serum transaminases or creatinine, determined as levels being > 5 times upper limit of normal.
• Active hepatobiliary or hepatic disease (Non B Chronic Hepatitis B/C co-infection is allowed).
• CD4 cell count > 350 cells/mm3.