Testing for Tuberculosis in the United Kingdom HIV Infected Population

NCT02712671 | Unknown

• 1 other identifier: UCL 12/0212
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Human Immunodeficiency Virus (HIV) is the strongest individual risk factor for the reactivation of tuberculosis (TB) after previous exposure to Mycobacterium tuberculosis (MTb). This risk is reduced but not completely eliminated when HIV is treated with antiretroviral therapy (ART). Both the British HIV Association (BHIVA) and National Institute of Health and Care Excellence (NICE) suggest testing for latent TB infection in HIV infected individuals, but use different criteria. The cost -effectiveness of either approach has not been assessed, nor is testing widespread. A certain proportion of HIV infected subjects in Africa have MTb detectable in their sputum despite not having symptoms (such as cough or weight loss), nor changes on a chest x ray. It is unclear if this happens in lower TB prevalence areas such as the United Kingdom (UK). We intend to test a cohort of HIV infected subjects for evidence of latent TB using a tuberculin skin test (TST) and Interferon Gamma Release Assay (IGRA), ask about symptoms (using a standardised questionnaire) and to induce sputum using a saline nebuliser, to detect MTb using microscopy and culture, and newer nucleic acid amplification (genetic) techniques. Some patients, despite being exposed to TB in the past, will not mount a response using an IGRA or TST, which maybe due to an abnormal immune response. This lack of response seems more common in HIV. By investigating the number of patients with positive TST, IGRA, chest X ray and evidence of MTb in their sputum, in the context of place of birth, previous exposure to TB, CD4 count and other medications, we can assess the cost- effectiveness of systematic TB screening and the use anti-TB antibiotics to prevent reactivation of TB. In time, we will be able to answer important questions about the time taken to reactivate TB in individuals with HIV who do or don't take preventative anti-TB medications in the UK.

Conditions

HIV; Latent Tuberculosis

Keywords

Cost-Benefit Analysis; Quality of Life

Outcome Measures

Primary Outcomes (3)

• Number of cases of active tuberculosis disease

  Number of cases of active TB disease amongst the enrolled subjects, defined by the number of participants with X ray changes consistent with active tuberculosis and/or sputum culture positive for Mycobacterium tuberculosis with symptoms consistent with tuberculosis disease.

  1 year

• Number of cases of subclinical tuberculosis

  Number of cases of subclinical tuberculosis amongst the enrolled subjects, defined by the number of participants with sputum culture positive for Mycobacterium tuberculosis, with or without X ray changes consistent with active tuberculosis and without symptoms consistent with tuberculosis disease.

  1 year

• Number of cases latent tuberculosis infection

  Number of cases of latent tuberculosis infection amongst the enrolled subjects, defined by the number of participants with with positive tuberculin skin test (TST) and/or interferon gamma release assay (IGRA) (for latent TB infection), but without a history of previous, treated tuberculosis disease and without symptoms, X ray changes consistent with active tuberculosis disease or sputum culture positive for Mycobacterium tuberculosis.

  1 year

Secondary Outcomes (7)

• Number with subsequent active TB disease

  20 years

• Time to subsequent active TB disease

  20 years

• Number of participants with a diagnosis of airways disease in an HIV infected cohort

  2 years

• Quality of life scores for those with HIV infection with or without TB infection.

  2 years

• Uptake of latent TB preventive treatment in an HIV clinic cohort

  2 years

Study Arms (1)

Enrolled subjects

Subjects attending the Ian Charleson Centre and agreeing to be tested for latent, subclinical and active tuberculosis using Chest radiograph, Blood interferon gamma release assay, Tuberculin skin testing, Sputum induction for mycobacterial microscopy and culture with spirometry, and Mycobacterium tuberculosis polymerase chain reaction testing.

Radiation: Chest radiograph; Procedure: Blood interferon gamma release assay; Procedure: Tuberculin skin testing (TST); Procedure: Sputum induction for mycobacterial microscopy and culture; Other: Mycobacterium tuberculosis polymerase chain reaction testing; Procedure: Spirometry

Interventions

Chest radiograph RADIATION

A chest radiograph involves the participant standing in front of a film and a low dose of radiation passes through the chest. This will be used to look for evidence of tuberculosis infection.

Also known as: Chest X ray

Enrolled subjects

Blood interferon gamma release assay PROCEDURE

Test of T-lymphocytes' response to exposure with tuberculosis antigens. This test is used for the diagnosis of latent tuberculosis infection and involves a blood sample in lithium heparin tube. It will be performed in an off site laboratory (Oxford Immunotec, Abingdon, Oxfordshire, United Kingdom).

Also known as: Blood IGRA, TSpot.TB

Enrolled subjects

Tuberculin skin testing (TST) PROCEDURE

An intradermal test for latent tuberculosis infection that involves a small injection of purified protein derivative (PPD) from inactivated Mycobacterium tuberculosis. The reaction is interpreted at 48-72 hours by measuring the induration produced.

Also known as: TST, Mantoux test

Enrolled subjects

Sputum induction for mycobacterial microscopy and culture PROCEDURE

Participants will breathe in a nebuliser salt solution (3.5% normal saline) for 15 minutes and asked to cough up a sputum sample. This is undertaken in a negative pressure tent. The sample will be tested for mycobacteria under the microscope and then cultured for 42 days in liquid culture bottles the microbiology laboratory.

Enrolled subjects

Mycobacterium tuberculosis polymerase chain reaction testing OTHER

Sputum from sputum induction will be tested using the GeneXpert system using polymerase chain reaction to identify genes present in Mycobacterium tuberculosis. This test is performed in a microbiology laboratory and tests for the presence of Mycobacterium tuberculosis in sputum, plus genes associated with drug resistance.

Also known as: TB PCR, GeneXpert MTB/RIF

Enrolled subjects

Spirometry PROCEDURE

Participants will be asked to blow into a spirometer to measure how much air they can expel in one second and in a whole breath. This will be repeated six times (three times before inhaling 3.5% saline solution and three times five minutes after breathing 3.5% saline solution). The results will be used to identify those whose airways are sensitive to the solution and to look for the presence of airways disease (asthma or chronic obstructive pulmonary disease).

Also known as: Lung function

Enrolled subjects

Eligibility Criteria

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

Study Population

Patients attending an ambulatory clinic for Human Immunodeficiency Virus (HIV) care in London.

You may qualify if:

• New diagnosis of HIV or established in care in HIV clinic by stratified sampling
• Able to give informed consent

You may not qualify if:

• Diagnosis of active TB or undergoing treatment for active or latent TB
• Inability to produce sputum by coughing (e.g. recent rib fracture, chest pain, pneumothorax)
• Pregnancy
• Use of steroids (equivalent to 15mg prednisolone for ≥4 weeks) or any other immunosuppressive drugs (e.g. azathioprine) - relative
• Active solid organ or haematological malignancy (excluding Kaposi's sarcoma)
• Previous hypersensitivity to purified protein derivative (PPD)
• Extensive eczema

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

Ian Charleson Centre, Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood plasma and serum

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

X-Rays; Culture Techniques; Ventilation

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; In Vitro Techniques; Investigative Techniques; Environment, Controlled; Environment; Environment and Public Health

Study Officials

• Marc Lipman, MD

  Clinical Senior Lecturer and Consultant Physician

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2016
• First Posted: March 18, 2016
• Study Start: June 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: September 1, 2024
• Last Updated: May 31, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)