Observational Study of Specificity of Mycobacterium Tuberculosis Screening and Diagnostics in HIV-Infected Individuals

Sensitivity and Specificity of Mycobacterium Tuberculosis Screening and Diagnostics in HIV-Infected Individuals

An estimated 3 million HIV-infected individuals will enter programs for antiretroviral (ARV) treatment in the coming year, with projected rates of requirement for ARV therapy extending to more than 10 million in sub-Saharan Africa, southeastern Asia, and Latin America in the coming decade. In these settings, Tuberculosis (TB) is an endemic infection in the population, and an estimated 30-60% of adults have been infected with TB, the leading opportunistic infection associated with HIV infection. The purpose of this study is to construct a standardized diagnostic evaluation (SDE) for TB that provides an increase in identification of participants with active pulmonary TB, without sacrificing specificity.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Tuberculosis
• Intervention / Treatment: Other: Standardized diagnostic evaluation

Detailed Description

Well developed TB diagnostic testing, contact tracing, and treatment programs are key parts of the public health and health care infrastructure in many countries where HIV infection has resulted in a 3- to 10-fold increase in clinical TB, accompanied by increasing HIV prevalence. The primary purpose of this study is to construct a standardized diagnostic evaluation (SDE) for TB that provides an increase in identification of participants with active pulmonary TB, without sacrificing specificity.

This observational study will include participants who are HIV-infected and TB-uninfected and not receiving ARV therapy. The duration of this trial will last between 1 and 14 days. Screening and study entry may occur at the same visit. All evaluations must be performed within 14 days after the participant is registered. Medical and medication history, physical exam, oral examination and swab, chest x-ray, sputum and blood collection, and documentation of PPD/TST (if available) will occur within this 14-day period.

• Study Type: Observational
• Enrollment (Actual): 801

Contacts and Locations

Study Locations

• Botswana
  • Gaborone, Botswana
    • Gaborone Prevention/Treatment Trials CRS
  • Molepolole, Botswana
    • Molepolole Prevention/Treatment Trials CRS (Molepolole PTT CRS)
• Brazil
  • Rio de Janeiro
    • Manguinhos, Rio de Janeiro, Brazil
      • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
• India
  • Maharashtra
    • Pune, Maharashtra, India, 411001
      • BJ Medical College CRS
    • Pune, Maharashtra, India, 411026
      • NARI Pune CRS
• Malawi
  • Lilongwe, Malawi
    • University of North Carolina Lilongwe CRS
• Peru
  • Lima, Peru, 18
    • Asociacion Civil Impacta Salud y Educacion - Miraflores, CRS
  • Lima
    • San Miguel, Lima, Peru
      • San Miguel CRS
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa
      • Wits HIV CRS
    • Johannesburg, Gauteng, South Africa, 1864
      • Soweto ACTG CRS
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4011
      • CAPRISA eThekwini CRS
    • Durban, KwaZulu-Natal, South Africa
      • Durban Adult HIV CRS
• Zimbabwe
  • Harare, Zimbabwe
    • UZ-Parirenyatwa CRS (30313)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

HIV-infected males and females who are not currently receiving ART

Description

Inclusion Criteria:

• HIV-infected

Exclusion Criteria:

• Receipt of ART within 90 days prior to study entry
• Diagnosis of active TB (pulmonary or extrapulmonary) within 90 days prior to study entry
• Receipt of 7 or more cumulative days of certain medications within 90 days prior to study entry. More information on this criterion can be found in the protocol.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; HIV-infected males and females who are not currently receiving ART	Other: Standardized diagnostic evaluation; Participants will undergo a diagnostic evaluation for TB at study entry; Other Names: SDE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effectiveness in creating a standard diagnostic evaluation for identification of participants with active pulmonary TB	Throughout study

Secondary Outcome Measures

Outcome Measure	Time Frame
Prevalence of TB in symptomatic and asymptomatic individuals	Throughout study
Rates of TB drug resistance	Throughout study
Feasibility and incremental benefits of diagnostic and screening evaluations over a range of CD4 cell counts	Throughout study
Value of oral candidiasis as a predictor of TB	Throughout study
Significance of investigational serologic assay when added to sputum acid-fast bacilli (AFB) smears when identifying participants with active TB compared to AFB smears alone	Throughout study
Storage of samples for future diagnostic and pathogenesis studies of mycobacterial, virologic, and immunologic factors	Throughout study

Collaborators and Investigators

• Sponsor: AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Dental and Craniofacial Research (NIDCR)
• Investigators: Study Chair: Susan Swindells, MBBS, University of Nebraska; Study Chair: Srikanth Tripathy, MBBS, National AIDS Research Institute, MIDC, Bhosari

Publications and helpful links

General Publications

• Aichelburg MC, Rieger A, Breitenecker F, Pfistershammer K, Tittes J, Eltz S, Aichelburg AC, Stingl G, Makristathis A, Kohrgruber N. Detection and prediction of active tuberculosis disease by a whole-blood interferon-gamma release assay in HIV-1-infected individuals. Clin Infect Dis. 2009 Apr 1;48(7):954-62. doi: 10.1086/597351.
• Ani AE. Advances in the laboratory diagnosis of Mycobacterium tuberculosis. Ann Afr Med. 2008 Jun;7(2):57-61. doi: 10.4103/1596-3519.55680.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 17, 2009
• First Posted (Estimate): March 19, 2009

Study Record Updates

• Last Update Posted (Estimate): March 18, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Pulmonary Tuberculosis; Myobacterium Infections
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: ACTG A5253; 1U01AI068636 (U.S. NIH Grant/Contract)