Screening for Tuberculosis in HIV-infected Patients Eligible for Antiretroviral Treatment

NCT01433796 | Completed

• 2 other identifiers: LU-2010/6723120/215/03
• Study Type: observational
• Target: 812
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

HIV Infection; Tuberculosis

Keywords

antiretroviral therapy; tuberculosis; health centres; Ethiopia

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (1)

• Comparison of diagnostic methods for detection of TB among HIV-infected subjects eligible to start ART.

  Two years

Study Arms (1)

Antiretroviral therapy, tuberculosis

Patients eligible for starting ART in health centres in Ethiopia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

HIV-infected patients managed in health centres

You may qualify if:

• 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

You may not qualify if:

• Ongoing or previous antiretroviral therapy
• Treatment for active tuberculosis for more than two weeks

Sponsors & Collaborators

• Lund University: lead
• Swedish International Development Cooperation Agency (SIDA): collaborator

Study Sites (5)

Adama Health Centre

Ādama, Oromiya, Ethiopia

Location

Geda Health Centre

Ādama, Oromiya, Ethiopia

Location

Dhera Health Center

Dhera, Oromiya, Ethiopia

Location

Mojo Health Centre

Mojo, Oromiya, Ethiopia

Location

Welenchiti Health Centre

Welenchiti, Oromiya, Ethiopia

Location

Related Publications (15)

• 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.

  PMID: 18784453 BACKGROUND

• World Health Organization. Global tuberculosis control: epidemiology, strategy, financing. WHO Report, 2009. Geneva: World Health Organization, 2009

  BACKGROUND

• 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. doi: 10.1164/rccm.200606-759OC. Epub 2006 Sep 14.

  PMID: 16973982 BACKGROUND

• 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.

  PMID: 19223783 BACKGROUND

• 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.

  PMID: 20825313 BACKGROUND

• 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.

  PMID: 11741165 BACKGROUND

• 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.

  PMID: 20181971 BACKGROUND

• 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. doi: 10.1097/QAD.0b013e328011efac.

  PMID: 17255740 BACKGROUND

• 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. doi: 10.1086/503437. Epub 2006 Apr 4.

  PMID: 16619192 BACKGROUND

• 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. doi: 10.1097/00002030-200312050-00008.

  PMID: 14685055 BACKGROUND

• Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. September 2009 progress report. WHO 2009

  BACKGROUND

• Balcha TT, Skogmar S, Sturegard E, Schon T, Winqvist N, Reepalu A, Jemal ZH, Tibesso G, Bjork J, Bjorkman P. A Clinical Scoring Algorithm for Determination of the Risk of Tuberculosis in HIV-Infected Adults: A Cohort Study Performed at Ethiopian Health Centers. Open Forum Infect Dis. 2014 Oct 10;1(3):ofu095. doi: 10.1093/ofid/ofu095. eCollection 2014 Dec.

  PMID: 25734163 DERIVED

• Reepalu A, Balcha TT, Skogmar S, Jemal ZH, Sturegard E, Medstrand P, Bjorkman P. High rates of virological suppression in a cohort of human immunodeficiency virus-positive adults receiving antiretroviral therapy in ethiopian health centers irrespective of concomitant tuberculosis. Open Forum Infect Dis. 2014 Jun 19;1(1):ofu039. doi: 10.1093/ofid/ofu039. eCollection 2014 Mar.

  PMID: 25734107 DERIVED

• Reepalu A, Balcha TT, Skogmar S, Jemal ZH, Sturegard E, Medstrand P, Bjorkman P. High rates of viral suppression in a cohort of HIV-positive adults receiving ART in Ethiopian health centers irrespective of concomitant tuberculosis. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19612. doi: 10.7448/IAS.17.4.19612. eCollection 2014.

  PMID: 25394116 DERIVED

• Balcha TT, Sturegard E, Winqvist N, Skogmar S, Reepalu A, Jemal ZH, Tibesso G, Schon T, Bjorkman P. Intensified tuberculosis case-finding in HIV-positive adults managed at Ethiopian health centers: diagnostic yield of Xpert MTB/RIF compared with smear microscopy and liquid culture. PLoS One. 2014 Jan 22;9(1):e85478. doi: 10.1371/journal.pone.0085478. eCollection 2014.

  PMID: 24465572 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Aliquoted plasma samples from consenting participants are stored at -80 C for analysis of biomarkers of tuberculosis and for prognostic markers. Stool and urine samples are stored at -20 C for analysis of alternative biomarkers of active tuberculosis.

MeSH Terms

Conditions

HIV Infections; Tuberculosis

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• Per Björkman, M.D., Associate professor

  Lund University

  STUDY DIRECTOR

• Taye Tolera Balcha, M.D.

  Lund University

  PRINCIPAL INVESTIGATOR

• Erik Sturegård, M.D., Ph.D.

  Lund University

  STUDY CHAIR

• Patrik Medstrand, Professor

  Lund University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: September 11, 2011
• First Posted: September 14, 2011
• Study Start: October 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: December 1, 2015
• Last Updated: March 8, 2016

Record last verified: 2016-03

Locations

ET (5)