Gene Expression in HIV and Tuberculosis Co-infection

NCT01611402 | Completed

• 2 other identifiers: 12014212-I-0142
• Study Type: observational
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis

Keywords

Tuberculosis; HIV Infection; Transcriptional Signature; IRIS

Outcome Measures

Primary Outcomes (1)

• Identify blood mRNA expression profiles distinguishing TB onoinfectedfrom TB/HIV co-infected patients (ART-naive and ART-treated with and without TB-IRIS).

  During data analysis phase

Secondary Outcomes (3)

• Correlate gene expression levels with clinical and laboratory variablesincluding flow cytometry and soluble biomarkers.

  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...

  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.

  During data analysis phase

Eligibility Criteria

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

You may qualify if:

• 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.
• Ability and willingness of subject or legal guardian/representative to understand study requirements and give informed consent. In the event an adult subject is unable, due to illness or mental incapacity, to give informed consent, a person authorized with durable power of attorney (DPA) or legal guardian may give consent for the subject s blood to be obtained, shipped, and tested under this protocol.
• 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 (Group A1) or
• Currently on TB therapy for \>7 days and \< 5 months (Group A2)
• 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

You may not qualify if:

• Pregnancy or post-partum period (6 months post-partum or while breast-feeding, whichever is longer).
• Documented history of hemoglobin from most recent blood draw less than 7g/dL.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Meintjes G, Rabie H, Wilkinson RJ, Cotton MF. Tuberculosis-associated immune reconstitution inflammatory syndrome and unmasking of tuberculosis by antiretroviral therapy. Clin Chest Med. 2009 Dec;30(4):797-810, x. doi: 10.1016/j.ccm.2009.08.013.

  PMID: 19925968 BACKGROUND

• Harries AD, Zachariah R, Corbett EL, Lawn SD, Santos-Filho ET, Chimzizi R, Harrington M, Maher D, Williams BG, De Cock KM. The HIV-associated tuberculosis epidemic--when will we act? Lancet. 2010 May 29;375(9729):1906-19. doi: 10.1016/S0140-6736(10)60409-6. Epub 2010 May 18.

  PMID: 20488516 BACKGROUND

• Houben RM, Crampin AC, Ndhlovu R, Sonnenberg P, Godfrey-Faussett P, Haas WH, Engelmann G, Lombard CJ, Wilkinson D, Bruchfeld J, Lockman S, Tappero J, Glynn JR. Human immunodeficiency virus associated tuberculosis more often due to recent infection than reactivation of latent infection. Int J Tuberc Lung Dis. 2011 Jan;15(1):24-31.

  PMID: 21276292 BACKGROUND

MeSH Terms

Conditions

Tuberculosis; HIV Infections

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Irini Sereti, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2012
• First Posted: June 5, 2012
• Study Start: May 29, 2012
• Study Completion: April 6, 2016
• Last Updated: April 5, 2018

Record last verified: 2016-04-06

Locations

US (1)