Gene Expression in HIV and Tuberculosis Co-infection
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Background:
- Tuberculosis (TB) infection is particularly deadly when it happens in people who are also infected with the human immunodeficiency virus (HIV). However, not much is known about how these two infections affect each other. Some people who have HIV or TB infections develop health problems after they start taking either HIV or TB medications or both. These drugs can improve the body's ability to fight infections, but sometimes this sudden improvement can make the infected person initially become sicker. Researchers want to study how these infections affect the immune system and the gene expression of people who have TB and may or may not have HIV, to see if there is a pattern of gene expression that may predict whether people starting treatment may get sicker initially.
Objectives:
- To study the gene expression and immune systems of people with TB who may or may not also have HIV.
Eligibility:
- Adults at least 18 years of age who have tuberculosis.
- Participants will be drawn from study sites in the United States and China.
Design:
- Participants will be divided into three study groups. The first group will have TB but not HIV. The second group will have both TB and HIV that have not been treated. The third group will have both TB and HIV that are currently being treated.
- All participants will have a single study visit. Blood samples will be collected at this visit. A medical history will also be collected.
- No treatment will be provided as part of this study.
Condition |
---|
Tuberculosis HIV IRIS |
Study Type: | Observational |
Study Design: | Time Perspective: Prospective |
Official Title: | Transcriptional Signature of HIV And TB Co-Infection |
Estimated Enrollment: | 200 |
Study Start Date: | May 2012 |
Tuberculosis (TB) remains one of the deadliest infections throughout the world, particularly in the setting of HIV infection. In China, TB is a frequently diagnosed complication of HIV infection. The immunopathogenesis of TB remains unclear, and although it is known that HIV infection increases the risk of developing active TB, either through infection or reactivation of latent disease, how it does so has yet to be determined. It is also known that patients co-infected with HIV and TB and na ve to antiretroviral therapy (ART) have a particularly high risk of developing Immune Reconstitution Inflammatory Syndrome (IRIS) after ART therapy is initiated, but the immunopathogenesis of this reaction is also unclear. The use of genomics has significantly improved the understanding of disease pathogenesis and is increasingly being used to predict responses to therapy as well. Recently, blood transcriptional signatures capable of distinguishing active and latent TB infection have been identified using highly parallelized analytical platforms capable of simultaneous survey of transcription of known genes. These signatures have hinted at a complex role for type I interferons in the development of active TB infection, but this has not yet been studied in people with HIV and TB co-infection. Further in depth studies are needed to characterize the spectrum of responses to TB/HIV co-infection, and how these responses correlate with clinical data. We propose a cross-sectional cohort study, to be conducted in both the US and in China, to identify blood mRNA expression profiles distinguishing TB mono-infected and TB/HIV co-infected ART-na ve patients from treated patients with and without TB-IRIS. Secondary objectives will include correlating gene expression levels with clinical outcomes and soluble biomarkers. The study will comprise a test set (in China) of 110 patients divided among the different cohorts and a validation set (in the US) of approximately 50 patients divided among the three groups. Participation will involve a single study visit to consist of small volume phlebotomy (approximately 25 mL for safety labs, transcriptome analysis, lymphocyte counts, and plasma storage) and information gleaned from the clinical record entered into a coded Case Report Form (CRF). The study will exclude persons who cannot provide informed consent, women who are pregnant or breast-feeding (which can be associated with immune compromise and changes in markers associated with inflammation), and persons with anemia (who may be unable to tolerate phlebotomy solely for research purposes).
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Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
For all patients:
Adults, age 18 or older
TB diagnosis, ascertained as follows:
- specimen or biopsy smear, culture, or PCR positivity or
compatible clinical presentation and imaging with strong suspicion for TB that necessitates initiation of empiric TB therapy (in which case the confirmation by culture or other laboratory means may follow enrollment, or alternatively clinical improvement in response to TB therapy may confirm the diagnosis).
If the TB diagnosis cannot be confirmed as above (i.e. culture positive for NTM), the patient will be excluded from final analysis.
Capable of understanding and providing informed consent
Agree to storage of study data and biologic specimens for use in future studies of immune function, tuberculosis, genetics, and/or HIV pathogenesis.
Patients in TB mono-infected arm (Group A) would additionally be eligible if:
HIV negative (documented seronegative within 1 month of study visit)
Not receiving TB therapy for more than 7 days prior to study visit
Patients in TB/HIV co-infected arm (Group B) would additionally be eligible if:
HIV positive (outside HIV testing will be accepted)
Not receiving TB therapy for more than 7 days prior to study visit
Untreated or ART na ve (will be accepted if they had been on ART in the past but none within the last 6 months).
Patients in TB/HIV co-infected, treated arm (Group C) would additionally be eligible if:
HIV positive
Currently receiving TB therapy
Currently receiving ART (The subset of patients without TB-IRIS will have been on antiretroviral therapy for at least 8 and not more than 12 weeks. The subset of patients with TB-IRIS will be enrolled at the time of their TB-IRIS event) with some evidence of adherence (often measured by clinical improvement, medication refills or laboratory values)
The TB-IRIS subset of patients (10 patients at NIAID and 20 patients at SHAPHC) would also need to meet criteria for paradoxical TB-IRIS
EXCLUSION CRITERIA:
Pregnancy or post-partum period (6 months post-partum or while breast-feeding, whichever is longer).
Unable to provide informed consent.
Documented history of hemoglobin from most recent blood draw less than 7g/dL.
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Contact: Eleanor M Wilson, M.D. | (301) 496-8019 | wilsonele@mail.nih.gov |
United States, District of Columbia | |
MedStar Health Institutions - Washington Hospital Center | Recruiting |
Washington, District of Columbia, United States | |
DC Tuberculosis and Chest Clinic | Recruiting |
Washington, District of Columbia, United States, 20003 | |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 | |
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 prpl@mail.cc.nih.gov | |
Dennis Avenue Health Center/ Montgomey Co. TB Clinic | Recruiting |
Silver Spring, Maryland, United States, 20902 | |
China | |
Shanghai Public Health Clinical Center | Recruiting |
Jinshan District, China |
Principal Investigator: | Eleanor M Wilson, M.D. | National Institute of Allergy and Infectious Diseases (NIAID) |
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Additional Information:
Publications:
ClinicalTrials.gov Identifier: | NCT01611402 History of Changes |
Other Study ID Numbers: | 120142, 12-I-0142 |
Study First Received: | June 1, 2012 |
Last Updated: | February 13, 2013 |
Health Authority: | United States: Federal Government |
Keywords provided by National Institutes of Health Clinical Center (CC):
Tuberculosis HIV Infection Transcriptional Signature IRIS |
Additional relevant MeSH terms:
Tuberculosis Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections |
ClinicalTrials.gov processed this record on March 03, 2013