Tuberculosis Recurrence Upon Treatment With Highly Active Antiretroviral Therapy (TRuTH)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01539005|
Recruitment Status : Completed
First Posted : February 27, 2012
Last Update Posted : February 2, 2017
|Condition or disease|
- Objective: To determine the extent of and reasons for relapse and re-infection in incident cases of tuberculosis (TB) in Human Immunodeficiency Virus (HIV)-infected patients on Highly Active Antiretroviral Therapy (HAART)
- Design: A prospective cohort study of patients with HIV previously treated for pulmonary TB and initiated on HAART in the SAPIT (Starting AIDS treatment at three Points in TB treatment) and START (Starting Tuberculosis and Anti-Retroviral Therapy) trials. Each incident case of TB recurrence in this cohort of adult patients on HAART will be investigated to assess whether the infecting mycobacterium is similar to that from the previous infection and whether the immune responses differ in cases of relapse and re-infection.
- Population: Men and women 18 years of age with documented HIV infection and past TB therapy as part of the SAPIT and START trial will be enrolled.
- Study Procedures: This study will involve 3 years of follow-up of patients who had been initiated on a course of TB therapy as part of the SAPIT and START trials. Upon exit from the SAPIT trial (i.e. 18 months post-TB diagnosis), study patients will be consented and enrolled in this cohort study. Study participants will be seen monthly for the first 3 months and thereafter 3 monthly, for routine clinic visits and ART services. At every visit patients will be screened for TB recurrence clinically, with chest radiograph and, whenever possible, with available TB diagnostics or new diagnostics that are being developed and/or tested.
- Study Outcome The primary endpoint of this study will be the development of recurrent TB. TB recurrence as a result of relapse will be defined as isolates of M. tuberculosis from the first and second episodes of TB which cluster in Restriction Fragment Length Polymerization (RFLP) analysis. TB recurrence as a result of re-infection will be defined as isolates from the first and second episode of TB which differ on RFLP analysis. Each study participant who has recurrent TB will be assessed by Interferon (IFN) gamma ELISPOT assay to compare cytotoxic lymphocyte (CTL)immune responses in TB relapse and re-infection.
|Study Type :||Observational|
|Actual Enrollment :||402 participants|
|Official Title:||Is Tuberculosis Recurrence in Treated Tuberculosis-Human Immunodeficiency Virus (HIV) Co-Infected Patients Relapse or Re-infection?|
|Study Start Date :||November 2009|
|Actual Primary Completion Date :||April 23, 2014|
|Actual Study Completion Date :||April 23, 2014|
- Tuberculosis [ Time Frame: Tuberculosis case finding will be conducted over a 36 month period. Tuberculosis investigations will be conducted from the date of Enrollment to the date of TB diagnosis based on a positive sputum TB culture ]The primary endpoint of this study will be development of TB. TB recurrence as a result of relapse will be defined as isolates of M.tuberculosis from the first and second episodes of TB which cluster in Restriction Fragment Length Polymerization analysis. TB recurrence as a result of re-infection will be defined as isolates from the first and second episode of TB which differ on RFLP analysis. To detect TB, patients will have a sputum smear at every study visit. Chest X-Ray and safety bloods are conducted 6-monthly.
Biospecimen Retention: Samples With DNA
Stored Plasma/Serum/PBMCs: Participants who consent to have additional samples stored for future testing will have serum, plasma and PBMCs stored . Possible uses of plasma include assessment of host genetics profiles, including HLA profile, additional viral load assays.Possible uses of serum include additional safety serology and evaluation of suspected IRIS on participants where indicated. The PBMCs will be used to test for IRIS/PR when suspected.
Other potential tests that may be performed on the stored specimens include new generation assays of immunity.
Stored Sputum Isolates :RFLP testing will be performed from stored bacterial isolates on all positive cultures in which recurrence is suspected and compared to the initial positive culture used to diagnose the TB initially.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01539005
|CAPRISA eThekwini Clinical Research Site|
|Durban, KwaZulu Natal, South Africa, 4001|
|Principal Investigator:||Kogieleum Naidoo, MBChB||Centre for the AIDS Programme of Research in South Africa|
|Principal Investigator:||Salim S Abdool Karim, MBChB, PhD||Centre for the AIDS Programme of Research in South Africa|