Simultaneous Versus Sequential Antiretroviral Therapy (ARV) Therapy and Mycobacterium Tuberculosis (MTB) Treatment

Efficacy of Simultaneous Versus Sequential Antiretroviral Therapy and Antituberculosis Treatment in Patients With AIDS and Active Tuberculosis. Open, Randomized and Controlled, Multisite Clinical Trial.

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.

Study Overview

• Status: Terminated
• Conditions: HIV; Tuberculosis; AIDS
• Intervention / Treatment: Drug: Simultaneous ARV and antiMTB; Drug: Deferred RV and antiMTB treatment

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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • DF
    • Mexico city, DF, Mexico, 14080
      • Centro de Investigaciones en Enfermedades Infecciosas
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 45235
      • Hospital Civil de Guadalajara Fray Antonio Alcalde

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Receives both, simultaneously antiretroviral therapy and antituberculosis therapy	Drug: Simultaneous ARV and antiMTB; Receives both, simultaneously antiretroviral therapy and antituberculosis therapy; Other Names: Truvada; HAART; isoniazid; Efavirenz
Experimental: Group 2; Receives only antituberculosis therapy, and 2 months afterwards antiretroviral therapy	Drug: Deferred RV and antiMTB treatment; Receives only antituberculosis therapy and 2 months afterwards antiretroviral therapy; Other Names: Truvada; HAART; isoniazid; Efavirenz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to remission of signs and symptoms of active tuberculosis as well as general symptoms.	96 wk
Time to negative measurement of mycobacterial load in body fluids or affected tissues	24 wk

Secondary Outcome Measures

Outcome Measure	Time Frame
CD4+ cell count increase	24 wk
Lymphoproliferative response to specific antigens against Mtb	24 wk
Time to undetectable HIV plasma load; HIV genotype	24 wk

Collaborators and Investigators

• Sponsor: Instituto Nacional de Enfermedades Respiratorias
• Collaborators: Consorcio de Investigación sobre VIH/SIDA/TB (CISIDAT).
• Investigators: Principal Investigator: Gustavo Reyes-Terán, MD, Instituto Nacional de Enfermedades Respiratorias

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• de Jong BC, Israelski DM, Corbett EL, Small PM. Clinical management of tuberculosis in the context of HIV infection. Annu Rev Med. 2004;55:283-301. doi: 10.1146/annurev.med.55.091902.103753.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Lawn SD, Bekker LG, Wood R. How effectively does HAART restore immune responses to Mycobacterium tuberculosis? Implications for tuberculosis control. AIDS. 2005 Jul 22;19(11):1113-24. doi: 10.1097/01.aids.0000176211.08581.5a.
• Orlovic D, Smego RA Jr. Paradoxical tuberculous reactions in HIV-infected patients. Int J Tuberc Lung Dis. 2001 Apr;5(4):370-5.

Helpful Links

• Consortium for HIV/TB Research in Mexico

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: August 19, 2008
• First Submitted That Met QC Criteria: August 19, 2008
• First Posted (Estimate): August 20, 2008

Study Record Updates

• Last Update Posted (Estimate): March 26, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Enzyme-Linked ImmunoSpot; Deferred treatment; Immune Recovery Inflammatory Syndrome
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fatty Acid Synthesis Inhibitors; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz; Isoniazid
• Other Study ID Numbers: C43-06