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

Phase 2
Conditions
Tuberculosis
HIV Infections
Registration Number
NCT00474435
Lead Sponsor
African Poverty Related Infection Oriented Research Initiative
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Pharmacokinetic parameters of emtricitabine, tenofovir and efavirenzTwo 24 hour pharmacokinetic (PK) curves (week 8 and 28)
Pharmacokinetic parameters of the tuberculostatic agentsPharmacokinetic (PK) samples at 2 hours and 6 hours postdose (week 2 and 8)
Secondary Outcome Measures
NameTimeMethod
Biochemistry and haematology samples for safetySamples at screening, baseline, week 2, 4, 6, 8, 12, 16, 24, 28
Questioning about occurrence of adverse eventsAt baseline, week 2, 4, 6, 8, 12, 16, 24, 28
CD4 count and HIV-1 RNAAt screening, week 4, week 16 and week 28
Sputum staining and cultureAt screening, week 4, 8, and 28

Trial Locations

Locations (1)

Kibong'oto National Tuberculosis Hospital

🇹🇿

Moshi, Kilimanjaro Region, Tanzania

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