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

March 14, 2011 updated by: Karolinska Institutet

Randomized Clinical Trial to Determine the Most Appropriate Time to Start HIV Treatment in HIV & TB Coinfected Adults Being Treated for Tuberculosis.

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?

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

450

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Ethiopia
      • Addis Ababa, Ethiopia, P.O.Box 9086
        • Recruiting
        • Tikur Anbessa (Black Lion) Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Treatment
Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated four weeks after starting rifampicin based short course anti tuberculosis treatment
Other Names:
  • Treatment
Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated eight weeks after starting rifampicin based short course anti tuberculosis treatment.
Other Names:
  • Treatment
Active Comparator: Arm-B
Deferred Treatment Group-1
Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated one week after starting rifampicin based short course anti tuberculosis treatment.
Other Names:
  • Treatment
Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated four weeks after starting rifampicin based short course anti tuberculosis treatment
Other Names:
  • Treatment
Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated eight weeks after starting rifampicin based short course anti tuberculosis treatment.
Other Names:
  • Treatment
Active Comparator: Arm-C
Deferred Treatment Group-2
Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated one week after starting rifampicin based short course anti tuberculosis treatment.
Other Names:
  • Treatment
Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated four weeks after starting rifampicin based short course anti tuberculosis treatment
Other Names:
  • Treatment
Other: Comparison of different treatment strategies
600 mg efavirenz based HAART initiated eight weeks after starting rifampicin based short course anti tuberculosis treatment.
Other Names:
  • Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mortality
Time Frame: 24 weeks
all cause mortality
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tuberculosis-Immune Reconstitution Inflammatory Syndrome
Time Frame: 24 weeks
24 weeks
New AIDS defining clinical events
Time Frame: 24 weeks
24 weeks
Drug Induced Liver toxicity
Time Frame: 24 weeks
24 weeks
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
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Collaborators

Addis Ababa University

Investigators

  • Study Director: Eleni Aklillu, PhD, Krolinska Institutet, Stockholm, Sweden
  • Principal Investigator: Wondwossen Amogne, MD, Addis Ababa University, Addis Ababa, Ethiopia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2008

Primary Completion (Anticipated)

January 1, 2012

Study Completion (Anticipated)

March 1, 2012

Study Registration Dates

First Submitted

March 14, 2011

First Submitted That Met QC Criteria

March 14, 2011

First Posted (Estimate)

March 15, 2011

Study Record Updates

Last Update Posted (Estimate)

March 15, 2011

Last Update Submitted That Met QC Criteria

March 14, 2011

Last Verified

March 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SWE-2007-270

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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