Tuberculosis Clinical Trial
Official title:
Tuberculosis in HIV-infected Patients Managed in Health Centres in Ethiopia - Identification of a Screening Algorithm for Active Tuberculosis and Determination of Outcome of Combined Antituberculosis and Antiretroviral Treatment
Background: Increased access to antiretroviral therapy (ART) in Africa will require
decentralization to primary health care. For this purpose, adapted methods for management of
patients co-infected with tuberculosis (TB) and HIV are needed. Improved detection of TB in
patients starting ART, and assessment of co-administration of ART and TB treatment are
priorities in this field.
Aims: To identify clinical predictors of TB in patients starting ART, and to construct
screening algorithms for TB in this population; to assess ART outcomes in patients receiving
TB treatment at health centre level.
Work plan: The project is performed in health centres providing ART in Ethiopia. A cohort of
HIV positive patients initiating ART is prospectively followed. Baseline characteristics are
registered; blood samples for CD4 cells, HIV RNA and immunological markers are collected, as
well as sputum for TB culture and PCR. During ART, clinical data, CD4 cell counts and HIV
RNA levels are followed. Patients with TB are compared to those without TB with regard to
ART outcome. Baseline factors associated with TB will be used to construct TB screening
algorithms.
Recruitment of the cohort was completed in March 2013; follow-up for determination of long
term outcome of ART will be continued until 2016.
Significance: These studies give insight into TB-HIV co-infection at primary health care
level in a Sub-Saharan region, and may impact future guidelines for management of such
patients.
Status | Completed |
Enrollment | 812 |
Est. completion date | December 2015 |
Est. primary completion date | May 2013 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - HIV infection - Fulfills criteria for antiretroviral therapy (CD4 cell count below 350 cells/ml and/or WHO stage IV) - Residence in study uptake area - Written informed consent to participation and to tracing in case of defaulting Exclusion Criteria: - Ongoing or previous antiretroviral therapy - Treatment for active tuberculosis for more than two weeks |
Observational Model: Cohort, Time Perspective: Prospective
Country | Name | City | State |
---|---|---|---|
Ethiopia | Adama Health Centre | Adama | Oromia |
Ethiopia | Geda Health Centre | Adama | Oromia |
Ethiopia | Dhera Health Center | Dhera | Oromia |
Ethiopia | Mojo Health Centre | Mojo | Oromia |
Ethiopia | Welenchiti Health Centre | Welenchiti | Oromia |
Lead Sponsor | Collaborator |
---|---|
Lund University | Swedish International Development Cooperation Agency (SIDA) |
Ethiopia,
Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, Gengiah T, Nair G, Bamber S, Singh A, Khan M, Pienaar J, El-Sadr W, Friedland G, Abdool Karim Q. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010 Feb 25;362(8):697-706. doi: 10.1056/NEJMoa0905848. — View Citation
Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A, Jones M, O'Brien SM, Persing DH, Ruesch-Gerdes S, Gotuzzo E, Rodrigues C, Alland D, Perkins MD. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010 Sep 9;363(11):1005-15. doi: 10.1056/NEJMoa0907847. Epub 2010 Sep 1. — View Citation
Breen RA, Miller RF, Gorsuch T, Smith CJ, Ainsworth J, Ballinger J, Swaden L, Cropley I, Johnson MA, Lipman MC. Virological response to highly active antiretroviral therapy is unaffected by antituberculosis therapy. J Infect Dis. 2006 May 15;193(10):1437-40. Epub 2006 Apr 4. — 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
Hung CC, Chen MY, Hsiao CF, Hsieh SM, Sheng WH, Chang SC. Improved outcomes of HIV-1-infected adults with tuberculosis in the era of highly active antiretroviral therapy. AIDS. 2003 Dec 5;17(18):2615-22. — View Citation
Lawn SD, Harries AD, Anglaret X, Myer L, Wood R. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS. 2008 Oct 1;22(15):1897-908. doi: 10.1097/QAD.0b013e32830007cd. Review. — View Citation
Lawn SD, Myer L, Bekker LG, Wood R. Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa. AIDS. 2007 Jan 30;21(3):335-41. — View Citation
Shah S, Demissie M, Lambert L, Ahmed J, Leulseged S, Kebede T, Melaku Z, Mengistu Y, Lemma E, Wells CD, Wuhib T, Nelson LJ. Intensified tuberculosis case finding among HIV-Infected persons from a voluntary counseling and testing center in Addis Ababa, Ethiopia. J Acquir Immune Defic Syndr. 2009 Apr 15;50(5):537-45. doi: 10.1097/QAI.0b013e318196761c. — View Citation
Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. September 2009 progress report. WHO 2009
Wood R, Middelkoop K, Myer L, Grant AD, Whitelaw A, Lawn SD, Kaplan G, Huebner R, McIntyre J, Bekker LG. Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control. Am J Respir Crit Care Med. 2007 Jan 1;175(1):87-93. Epub 2006 Sep 14. — View Citation
World Health Organization. Global tuberculosis control: epidemiology, strategy, financing. WHO Report, 2009. Geneva: World Health Organization, 2009
* Note: There are 11 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Correlation between baseline clinical characteristics and presence of microbiologically confirmed active tuberculosis. | To develop an algorithm with the potential to identify indicators of prevalent and incident TB among patients initiating ART by correlating baseline clinical signs and symptoms with results of culture- and PCR-based investigations for TB. Such clinical characteristics will be compared both to TB present before starting ART, as well as to TB presenting during the first year after ART initiation. Results from this comparison will be used to construct an algorithm for TB screening in Ethiopian patients eligible for ART. | Two years | No |
Primary | Comparison of ART outcome in patients taking concomitant anti-tuberculosis therapy and those only taking ART. | To prospectively compare clinical, immunological and virological outcomes of ART in patients with concomitant ATT to those in patients only receiving ART. Specific aims are to study rates of virological suppression during ART, the development of antiretroviral drug resistance, and treatment adherence. | Three years | No |
Secondary | Comparison of diagnostic methods for detection of TB among HIV-infected subjects eligible to start ART. | To compare the diagnostic yields of GeneXpert PCR, smear microscopy and novel tests for the detection of TB among HIV-infected subjects in Ethiopia eligible to start ART, using mycobacterial culture as reference. | Two years | No |
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