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Optimal Time to Initiate Antiretroviral Therapy in HIV & TB Coinfected Adults Being Treated for Tuberculosis (TB-HAART)

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ClinicalTrials.gov Identifier: NCT01315301
Recruitment Status : Unknown
Verified March 2011 by Karolinska Institutet.
Recruitment status was:  Recruiting
First Posted : March 15, 2011
Last Update Posted : March 15, 2011
Sponsor:
Collaborator:
Addis Ababa University
Information provided by:
Karolinska Institutet

Study Description
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Brief Summary:

Aim of the study is to determine optimal time to initiate anti-retroviral therapy in HIV/TB co-infected patients who recently started treatment for Tuberculosis by comparing immediate versus deferred initiation of HAART.

The study will address the following questions;

  • Is it possible to reduce mortality rate and increase survival by early initiation of HAART during TB treatment with out compromising for adverse drug reaction, toxicity and immune reconstitution syndrome?
  • What is the risk/ benefit ratio between immediate versus deferred initiation of HAART during TB treatment with respect to safety/efficacy of TB and HIV co-treatment?
  • When is the most appropriate time to start HAART during TB treatment?

Condition or disease Intervention/treatment Phase
Acquired Immunodeficiency Syndrome Tuberculosis Other: Comparison of different treatment strategies Not Applicable

Detailed Description:

The study intends to determine the optimal time to start ART by comparing three treatment strategies of ART initiation in HIV/TB co-infected patients. Four hundred fifty newly diagnosed HIV infected patients with active TB and CD4 cell count < 200 cells/mm3 will be prospectively recruited to be assigned randomly in parallel into one of the three treatment groups (n=150 in each group) and HAART will be started at different time points as described below with extensive counseling and adherence support.

  • Arm-A (Immediate Treatment Group): Receipt of antiretroviral therapy one week after starting anti-TB treatment.
  • Arm-B (Deferred Treatment Group-1): Antiretroviral therapy will be initiated at the 4th week of starting anti-TB treatment (in the middle of the intensive phase TB treatment).
  • Arm-C (Deferred Treatment Group-2): Antiretroviral therapy will be initiated at the 8th week of starting anti-TB treatment (after completion of the intensive phase of TB treatment).

Study Design: Interventional, prospective, randomized, open-label three-armed trial with no placebo, Active control, parallel assignment, safety and efficacy study.

Study population: Previously untreated HIV-infected adult patients with TB and CD4 cell counts < 200/mm3 at the time of TB diagnosis.

Expected Total Enrollment = 450

Treatment: Patients will receive first-line preferred regimen for patients with TB and HIV coinfection (rifampicin containing short course TB treatment and efavirenz-containing HAART regimen. The intensive phase of anti-TB therapy consists of 2 months treatment with Rifampicin, Isoniazid, Pyrazinamide and Ethambutol followed by the continuation phase with Isoniazid and Rifampicin daily for 4 months under Directly Observed Therapy (DOTS). After the initiation of TB treatment, patients in Arm-A, Arm-B and Arm-C will start EFV-containing HAART regimen (efavirenz + Lamivudine (3TC) + Stavudine (d4T) after one week, in the middle(at 4th week) and at the end (8th week) of the intensive phase TB treatment respectively. Primar prophylaxis with cotrimoxazole will be offered to all patients.


Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Randomized Clinical Trial to Determine the Most Appropriate Time to Start HIV Treatment in HIV & TB Coinfected Adults Being Treated for Tuberculosis.
Study Start Date : August 2008
Estimated Primary Completion Date : January 2012
Estimated Study Completion Date : March 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Arm-A
Immediate Treatment Group
 Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated one week after starting rifampicin based short course anti tuberculosis treatment.
Other Name: Treatment
Active Comparator: Arm-B
Deferred Treatment Group-1
 Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated four weeks after starting rifampicin based short course anti tuberculosis treatment
Other Name: Treatment
Active Comparator: Arm-C
Deferred Treatment Group-2
 Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated eight weeks after starting rifampicin based short course anti tuberculosis treatment.
Other Name: Treatment


Outcome Measures
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Primary Outcome Measures :
  1. mortality [ Time Frame: 24 weeks ]
    all cause mortality


Secondary Outcome Measures :
  1. Tuberculosis-Immune Reconstitution Inflammatory Syndrome [ Time Frame: 24 weeks ]
  2. New AIDS defining clinical events [ Time Frame: 24 weeks ]
  3. Drug Induced Liver toxicity [ Time Frame: 24 weeks ]
  4. Virologic success [ Time Frame: 24 weeks ]
    Proportion of patients with Virologic success defined as achieving a viral load of < 50 HIV-1 RNA copies/mL within 6 months of starting therapy


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed ART naive HIV infected patients and age > 18 years old
  • Newly diagnosed smear +ve PTB cases (abnormal CXR and at least one sputum sample +ve for AFB)
  • Newly diagnosed smear -ve PTB cases (CXR consistent with active TB plus at least two sputum specimens negative for AFB and decision by the physician to treat for TB or smear negative for AFB but culture positive cases)
  • Tissue biopsy or FNAC results consistent with the diagnosis of tuberculosis
  • CD4 cell count < 200/mm3 at the time of TB diagnosis
  • Residence in Addis Ababa, Ethiopia
  • Ability to give signed written/thumb sign informed consent

Exclusion Criteria:

  • Pregnancy and breast-feeding women
  • Patients who received anti TB therapy with in the past two years
  • Patients who have previous treatment experience with antiretroviral therapy
  • Severely ill patients Karnofsky performance status score < 40
  • Baseline Hgb < 8 gms/dL
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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): NCT01315301


Contacts
Contact: Wondwossen Amogne, MD +251911406179 wonamogne@yahoo.com
Contact: Eleni Aklillu, PhD +46735116131 Eleni.aklillu@ki.se

Locations
Ethiopia
Tikur Anbessa (Black Lion) Hospital Recruiting
Addis Ababa, Ethiopia, P.O.Box 9086
Contact: Wondwossen Amogne, MD    +2519114046179    wonamogne@yahoo.com   
Contact: Eleni Aklillu, PhD    +47735116131    eleni.aklillu@ki.se   
Sponsors and Collaborators
Karolinska Institutet
Addis Ababa University
Investigators
Study Director: Eleni Aklillu, PhD Krolinska Institutet, Stockholm, Sweden
Principal Investigator: Wondwossen Amogne, MD Addis Ababa University, Addis Ababa, Ethiopia
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Eleni Aklillu,PhD, Associate Professor, Karolinska Institutet, Stockholm, Sweden
ClinicalTrials.gov Identifier: NCT01315301     History of Changes
Other Study ID Numbers: SWE-2007-270
First Posted: March 15, 2011    Key Record Dates
Last Update Posted: March 15, 2011
Last Verified: March 2011

Keywords provided by Karolinska Institutet:
Efavirenz
Rifampicin
HAART
Anti Tuberculosis

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Tuberculosis
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
 Slow Virus Diseases
Efavirenz
Rifampin
Antitubercular Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers