Simultaneous Versus Sequential Antiretroviral Therapy (ARV) Therapy and Mycobacterium Tuberculosis (MTB) Treatment
Primary Purpose
HIV, AIDS, Tuberculosis
Status
Terminated
Phase
Not Applicable
Locations
Mexico
Study Type
Interventional
Intervention
Simultaneous ARV and antiMTB
Deferred RV and antiMTB treatment
Sponsored by
About this trial
This is an interventional treatment trial for HIV focused on measuring Enzyme-Linked ImmunoSpot, Deferred treatment, Immune Recovery Inflammatory Syndrome
Eligibility Criteria
Inclusion Criteria:
- HIV infected
- < 200 CD4+ cells/mL
- Active pulmonary tuberculosis (with or without extrapulmonary involvement)
Exclusion Criteria:
- Meningeal tuberculosis
- Unable to attend 96 wk follow-up
Sites / Locations
- Centro de Investigaciones en Enfermedades Infecciosas
- Hospital Civil de Guadalajara Fray Antonio Alcalde
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group 1
Group 2
Arm Description
Receives both, simultaneously antiretroviral therapy and antituberculosis therapy
Receives only antituberculosis therapy, and 2 months afterwards antiretroviral therapy
Outcomes
Primary Outcome Measures
Time to remission of signs and symptoms of active tuberculosis as well as general symptoms.
Time to negative measurement of mycobacterial load in body fluids or affected tissues
Secondary Outcome Measures
CD4+ cell count increase
Lymphoproliferative response to specific antigens against Mtb
Time to undetectable HIV plasma load; HIV genotype
Full Information
NCT ID
NCT00737724
First Posted
August 19, 2008
Last Updated
March 24, 2015
Sponsor
Instituto Nacional de Enfermedades Respiratorias
Collaborators
Consorcio de Investigación sobre VIH/SIDA/TB (CISIDAT).
1. Study Identification
Unique Protocol Identification Number
NCT00737724
Brief Title
Simultaneous Versus Sequential Antiretroviral Therapy (ARV) Therapy and Mycobacterium Tuberculosis (MTB) Treatment
Official Title
Efficacy of Simultaneous Versus Sequential Antiretroviral Therapy and Antituberculosis Treatment in Patients With AIDS and Active Tuberculosis. Open, Randomized and Controlled, Multisite Clinical Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Terminated
Why Stopped
Other published trials showed definitive expected superiority of Group 1
Study Start Date
March 2008 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto Nacional de Enfermedades Respiratorias
Collaborators
Consorcio de Investigación sobre VIH/SIDA/TB (CISIDAT).
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate and compare the efficacy of immediate antiretroviral therapy versus 2 month deferred anti-Tb therapy upon the clinical course of tuberculosis and HIV infection in patients with AIDS and active tuberculosis.
Detailed Description
AIDS and tuberculosis are two international and national priority public health problems. The best time for starting antiretroviral therapy in patients with AIDS and active tuberculosis is not clear, despite of the guidelines regarding CD4+ count. The debate surrounding this issue is mainly due to the difficulty among adherence of anti-MTb and anti-HIV treatment, the pharmacological interaction, the adverse events related to drugs and the risk of inflammatory reconstitution syndrome, especially in patients with advanced HIV infection. Moreover, there is great debate upon the lack of knowledge of the degree of immune reconstitution throughout time against Mtb induced by the anti-HIV therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV, AIDS, Tuberculosis
Keywords
Enzyme-Linked ImmunoSpot, Deferred treatment, Immune Recovery Inflammatory Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
Receives both, simultaneously antiretroviral therapy and antituberculosis therapy
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Receives only antituberculosis therapy, and 2 months afterwards antiretroviral therapy
Intervention Type
Drug
Intervention Name(s)
Simultaneous ARV and antiMTB
Other Intervention Name(s)
HAART, isoniazid, Efavirenz, Truvada
Intervention Description
Receives both, simultaneously antiretroviral therapy and antituberculosis therapy
Intervention Type
Drug
Intervention Name(s)
Deferred RV and antiMTB treatment
Other Intervention Name(s)
HAART, isoniazid, Efavirenz, Truvada
Intervention Description
Receives only antituberculosis therapy and 2 months afterwards antiretroviral therapy
Primary Outcome Measure Information:
Title
Time to remission of signs and symptoms of active tuberculosis as well as general symptoms.
Time Frame
96 wk
Title
Time to negative measurement of mycobacterial load in body fluids or affected tissues
Time Frame
24 wk
Secondary Outcome Measure Information:
Title
CD4+ cell count increase
Time Frame
24 wk
Title
Lymphoproliferative response to specific antigens against Mtb
Time Frame
24 wk
Title
Time to undetectable HIV plasma load; HIV genotype
Time Frame
24 wk
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
HIV infected
< 200 CD4+ cells/mL
Active pulmonary tuberculosis (with or without extrapulmonary involvement)
Exclusion Criteria:
Meningeal tuberculosis
Unable to attend 96 wk follow-up
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gustavo Reyes-Terán, MD
Organizational Affiliation
Instituto Nacional de Enfermedades Respiratorias
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centro de Investigaciones en Enfermedades Infecciosas
City
Mexico city
State/Province
DF
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Hospital Civil de Guadalajara Fray Antonio Alcalde
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
45235
Country
Mexico
12. IPD Sharing Statement
Citations:
PubMed Identifier
1394786
Citation
Raviglione MC, Narain JP, Kochi A. HIV-associated tuberculosis in developing countries: clinical features, diagnosis, and treatment. Bull World Health Organ. 1992;70(4):515-26.
Results Reference
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PubMed Identifier
1518113
Citation
De Cock KM, Soro B, Coulibaly IM, Lucas SB. Tuberculosis and HIV infection in sub-Saharan Africa. JAMA. 1992 Sep 23-30;268(12):1581-7. doi: 10.1001/jama.268.12.1581.
Results Reference
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PubMed Identifier
7812542
Citation
Whalen C, Horsburgh CR, Hom D, Lahart C, Simberkoff M, Ellner J. Accelerated course of human immunodeficiency virus infection after tuberculosis. Am J Respir Crit Care Med. 1995 Jan;151(1):129-35. doi: 10.1164/ajrccm.151.1.7812542.
Results Reference
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PubMed Identifier
8757635
Citation
Goletti D, Weissman D, Jackson RW, Graham NM, Vlahov D, Klein RS, Munsiff SS, Ortona L, Cauda R, Fauci AS. Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation. J Immunol. 1996 Aug 1;157(3):1271-8.
Results Reference
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PubMed Identifier
8887603
Citation
Chaisson RE, Clermont HC, Holt EA, Cantave M, Johnson MP, Atkinson J, Davis H, Boulos R, Quinn TC, Halsey NA. Six-month supervised intermittent tuberculosis therapy in Haitian patients with and without HIV infection. Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1034-8. doi: 10.1164/ajrccm.154.4.8887603.
Results Reference
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PubMed Identifier
1898769
Citation
Small PM, Schecter GF, Goodman PC, Sande MA, Chaisson RE, Hopewell PC. Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection. N Engl J Med. 1991 Jan 31;324(5):289-94. doi: 10.1056/NEJM199101313240503.
Results Reference
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PubMed Identifier
11435232
Citation
Burman WJ, Jones BE. Treatment of HIV-related tuberculosis in the era of effective antiretroviral therapy. Am J Respir Crit Care Med. 2001 Jul 1;164(1):7-12. doi: 10.1164/ajrccm.164.1.2101133. No abstract available.
Results Reference
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PubMed Identifier
11741165
Citation
Dean GL, Edwards SG, Ives NJ, Matthews G, Fox EF, Navaratne L, Fisher M, Taylor GP, Miller R, Taylor CB, de Ruiter A, Pozniak AL. Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy. AIDS. 2002 Jan 4;16(1):75-83. doi: 10.1097/00002030-200201040-00010.
Results Reference
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PubMed Identifier
9655723
Citation
Narita M, Ashkin D, Hollender ES, Pitchenik AE. Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS. Am J Respir Crit Care Med. 1998 Jul;158(1):157-61. doi: 10.1164/ajrccm.158.1.9712001.
Results Reference
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PubMed Identifier
15990564
Citation
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PubMed Identifier
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Citation
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Citation
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Results Reference
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Links:
URL
http://www.cisidat.org.mx/
Description
Consortium for HIV/TB Research in Mexico
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Simultaneous Versus Sequential Antiretroviral Therapy (ARV) Therapy and Mycobacterium Tuberculosis (MTB) Treatment
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