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

HIV Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00737724
• Other study ID #: C43-06
• Status: Terminated
• Phase: N/A
• First received: August 19, 2008
• Last updated: March 24, 2015
• Start date: March 2008
• Est. completion date: February 2011

Study information

• Verified date: March 2015
• Source: Instituto Nacional de Enfermedades Respiratorias
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mexico: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 63
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• AIDS
• HIV
• Tuberculosis

Intervention

Drug:
• Simultaneous ARV and antiMTB
Receives both, simultaneously antiretroviral therapy and antituberculosis therapy
• Deferred RV and antiMTB treatment
Receives only antituberculosis therapy and 2 months afterwards antiretroviral therapy

Locations

Country	Name	City	State
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara	Jalisco
Mexico	Centro de Investigaciones en Enfermedades Infecciosas	Mexico city	DF

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Enfermedades Respiratorias	Consorcio de Investigación sobre VIH/SIDA/TB (CISIDAT).

Country where clinical trial is conducted

Mexico, 

References & Publications (12)

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. Review. — View 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. — View 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. Review. — View Citation

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. Review. — View 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. — View 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. — View Citation

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. — View 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. — View Citation

Orlovic D, Smego RA Jr. Paradoxical tuberculous reactions in HIV-infected patients. Int J Tuberc Lung Dis. 2001 Apr;5(4):370-5. Review. — View 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. Review. — View 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. — View 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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to remission of signs and symptoms of active tuberculosis as well as general symptoms.		96 wk	Yes
Primary	Time to negative measurement of mycobacterial load in body fluids or affected tissues		24 wk	No
Secondary	CD4+ cell count increase		24 wk	No
Secondary	Lymphoproliferative response to specific antigens against Mtb		24 wk	No
Secondary	Time to undetectable HIV plasma load; HIV genotype		24 wk	No

External Links

•   Consortium for HIV/TB Research in Mexico
•   Website of the sponsoring center