Gene Expression in HIV and Tuberculosis Co-infection
|ClinicalTrials.gov Identifier: NCT01611402|
Recruitment Status : Completed
First Posted : June 5, 2012
Last Update Posted : April 5, 2018
- 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.
- To study the gene expression and immune systems of people with TB who may or may not also have HIV.
- Adults at least 18 years of age who have tuberculosis.
- Participants will be drawn from study sites in the United States and China.
- 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 or disease|
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(SqrRoot) 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(SqrRoot) 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 up to 140 patients divided among the different cohorts and a validation set (in the US) of up to 125 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 serum and plasma storage) a urine sample and information gleaned from the clinical record entered into a coded Case Report Form (CRF). The U.S. cohort will have an additional 40 mLs of blood collected for mononuclear cells (total of approximately 65mLs).The study will exclude 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).
|Study Type :||Observational|
|Actual Enrollment :||96 participants|
|Official Title:||Transcriptional Signature of HIV And TB Co-Infection|
|Study Start Date :||May 29, 2012|
|Study Completion Date :||April 6, 2016|
- Identify blood mRNA expression profiles distinguishing TB onoinfectedfrom TB/HIV co-infected patients (ART-naive and ART-treated with and without TB-IRIS). [ Time Frame: During data analysis phase ]
- Correlate gene expression levels with clinical and laboratory variablesincluding flow cytometry and soluble biomarkers. [ Time Frame: During data analysis phase ]
- Quantify the tuberculosis antigen load at the beginning of anti-TB therapy by lateral flow lipo-arabinomannan assay (TB-LAM LFA) and study how the antigen burden affects the disease presentation (including radiographic findings), or transcriptio... [ Time Frame: During data analysis phase. ]
- Study separated cell populations (monocytes, dendritic cells, NK, T cell subsets or neurtrophils) to validate any identified transcriptional signature or to further investigate pathogen-specific responses. [ Time Frame: During data analysis phase ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01611402
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Irini Sereti, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|