Immediate Versus Deferred Start of Anti-HIV Therapy in HIV Infected Adults Being Treated for Tuberculosis - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00108862

Purpose

The purpose of this study is to determine the best time to begin anti-HIV treatment in individuals who have HIV and tuberculosis (TB).

Study hypothesis: Immediate antiretroviral therapy (ART), initiated within approximately 2 weeks after initiation of TB treatment, will reduce the frequency of other AIDS-defining illnesses and death in HIV infected participants being treated for TB by at least 40% by Week 48 when compared to deferred ART initiated at least 8 weeks after initiation of TB treatment.

Condition	Intervention
HIV Infections Tuberculosis	Drug: Efavirenz Drug: Emtricitabine Drug: Emtricitabine/Tenofovir disoproxil fumarate Drug: Tenofovir disoproxil fumarate Drug: Rifampin

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Strategy Study of Immediate Versus Deferred Initiation of Antiretroviral Therapy for HIV Infected Persons Treated for Tuberculosis With CD4 Less Than 200 Cells/mm3

Resource links provided by NLM:

MedlinePlus related topics: AIDS Tuberculosis

Drug Information available for: Rifampin Tenofovir Efavirenz Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Proportion of participants who have survived without AIDS progression [ Time Frame: Through Week 48 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	800
Study Start Date:	August 2006
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1A: Experimental Participants will initiate ART within 2 weeks after initiating TB treatment. Participants in Arm 1A will not enroll in Arm 2.	Drug: Efavirenz 600 mg tablet taken orally daily Drug: Emtricitabine 200 mg tablet taken orally daily Drug: Emtricitabine/Tenofovir disoproxil fumarate 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily Drug: Tenofovir disoproxil fumarate 300 mg tablet taken orally daily Drug: Rifampin Participants should continue receiving regimen that was prescribed prior to study entry
1B: Experimental Participants will defer ART until 8 to 12 weeks after initiation of their TB treatment. Participants will enroll in Arm 2 after completing Arm 1B.	Drug: Rifampin Participants should continue receiving regimen that was prescribed prior to study entry
2: Experimental Arm 1B participants will enroll in Arm 2 and initiate ART	Drug: Efavirenz 600 mg tablet taken orally daily Drug: Emtricitabine 200 mg tablet taken orally daily Drug: Emtricitabine/Tenofovir disoproxil fumarate 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily Drug: Tenofovir disoproxil fumarate 300 mg tablet taken orally daily Drug: Rifampin Participants should continue receiving regimen that was prescribed prior to study entry

Detailed Description:

TB is the most important coinfection in the HIV epidemic; the bi-directional relationship between the two diseases is well established. HIV increases the risk for TB acquisition, reactivation, and reinfection, and reduces survival compared to patients with TB alone. In individuals with HIV, TB infection results in reduced survival, increased risk for opportunistic infections, and elevations in HIV replication. Improving the outcome of HIV infected individuals who develop TB is of high importance. Initiating ART shortly after initiating TB treatment may improve outcomes in individuals coinfected with HIV and TB. However, data to support this suggestion are limited. This study will determine the most appropriate time to initiate ART in HIV infected individuals who recently initiated treatment for TB.

This study will last 48 weeks and will comprise two steps. At study entry, participants will undergo clinical assessment, drug adherence training, and blood collection. In Step 1, participants will be randomly assigned to one of two arms. Participants in Arm A will initiate ART within 2 weeks after initiating TB treatment.

Participants in Arm B will defer ART until 8 to 12 weeks after initiation of their TB treatment. In Step 2, Arm B participants will initiate ART; Arm A participants will not enter Step 2. ART will consist of efavirenz and emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC and TDF may be given as individual agents. Drug substitutions may be made for participants who cannot tolerate the specified regimen. Blood collection and clinical assessments will occur at Weeks 4, 8, 12, 16, 24, 32, 40, and 48.

Eligibility

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-infected
Confirmed or probable TB. More information on the criterion can be found in the protocol.
Chest x-ray within 30 days prior to study entry
Current rifampin- or other rifamycin-based TB treatment initiated within 14 days prior to study entry
CD4 count less than 200 cells/mm3 within 30 days prior to study entry
Willing to use acceptable methods of contraception while on study drugs and for 6 weeks after stopping these drugs
Able to swallow oral medications
Parent of guardian willing to provide informed consent, if applicable

Exclusion Criteria:

ART for longer than 7 days prior to study entry or treatment for any period of time with two or more antiretrovirals in combination. Participants who have taken nevirapine or zidovudine during pregnancy are not excluded.
Allergy or sensitivity to any of the study drugs or their formulations
History of multidrug-resistant TB
Receipt of any investigational therapy or chemotherapy within 30 days prior to study entry
Certain medications
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00108862

Show 22 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Diane Havlir, MD

San Francisco General Hospital and University of California, San Francisco

More Information

Additional Information:

Click here for information on efavirenz This link exits the ClinicalTrials.gov site

Click here for more information about emtricitabine This link exits the ClinicalTrials.gov site

Click here for more information about tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information about emtricitabine/tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

Teck R, Ascurra O, Gomani P, Manzi M, Pasulani O, Kusamale J, Salaniponi FM, Humblet P, Nunn P, Scano F, Harries AD, Zachariah R. WHO clinical staging of HIV infection and disease, tuberculosis and eligibility for antiretroviral treatment: relationship to CD4 lymphocyte counts. Int J Tuberc Lung Dis. 2005 Mar;9(3):258-62.

Kwara A, Flanigan TP, Carter EJ. Highly active antiretroviral therapy (HAART) in adults with tuberculosis: current status. Int J Tuberc Lung Dis. 2005 Mar;9(3):248-57.

[No authors listed] Combining TB treatment with HIV testing and treatment. J Adv Nurs. 2005 Mar;49(5):556. No abstract available.

Cahn P, Perez H, Ben G, Ochoa C. Tuberculosis and HIV: a partnership against the most vulnerable. J Int Assoc Physicians AIDS Care (Chic Ill). 2003 Jul-Sep;2(3):106-23. Review.

Williams BG, Dye C. Antiretroviral drugs for tuberculosis control in the era of HIV/AIDS. Science. 2003 Sep 12;301(5639):1535-7. Epub 2003 Aug 14.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5221, AACTG A5221
Study First Received:	April 19, 2005
Last Updated:	August 26, 2009
ClinicalTrials.gov Identifier:	NCT00108862 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Naive
TB
HIV
Antiretroviral Agents

Study placed in the following topic categories:

Bacterial Infections
Anti-Infective Agents
Efavirenz
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Antiviral Agents
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases
Rifampin

Gram-Positive Bacterial Infections
Anti-Retroviral Agents
Emtricitabine
HIV Infections
Sexually Transmitted Diseases
Tenofovir
Mycobacterium Infections
Tuberculosis
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Bacterial Infections
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Gram-Positive Bacterial Infections
Anti-Retroviral Agents
Emtricitabine
Therapeutic Uses
Tenofovir
Tuberculosis
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

Tenofovir disoproxil
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Actinomycetales Infections
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
Mycobacterium Infections

ClinicalTrials.gov processed this record on September 03, 2009