Impact of HIV Infection on Latent Tuberculosis (TB) Among Patients With HIV-TB Co-infection - Full Text View

Sponsor:	Ministry of Science and Technology, India
Collaborator:	Indian Council of Medical Research
Information provided by:	Ministry of Science and Technology, India
ClinicalTrials.gov Identifier:	NCT00692809

Purpose

HIV induced altered representation and function of regulatory T cell subsets (NKT and Treg cells) impair the protective T cell response against M.tuberculosis and disrupts LTBI, thus facilitates faster progression and development of severe forms of clinical TB in HIV-TB co-infection.

Condition
Latent Tuberculosis Infection HIV Infections Tuberculosis

Study Type:	Observational
Study Design:	Time Perspective: Prospective
Official Title:	Impact of HIV Infection on Latent TB Among Patients With HIV-TB Co-infection

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Tuberculosis

U.S. FDA Resources

Further study details as provided by Ministry of Science and Technology, India:

Primary Outcome Measures:

Precise component(s) of T cell response against M.tuberculosis compromised by HIV infection which leads to the development of severe forms of clinical tuberculosis. [ Time Frame: 5 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Elucidation of critical events of the cellular and molecular interactions that would be useful for developing newer therapeutic strategies and vaccination. [ Time Frame: 5 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	180
Study Start Date:	July 2008
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts
1 HIV+ve+LTBI (n=100)
2 HIV+ve+clinical TB (n=50)
3 HIV-ve+clinical TB (n=15)
4 Normal control (n=15)

Detailed Description:

During the natural course of HIV disease, emergence of opportunistic infection not only imposes morbidity on HIV-TB co-infected patients, but also facilitates viral replication causing faster disease progression. Tuberculosis, being the commonest among the opportunistic infections among HIV infected persons deserves special attention. Moreover, disruption of latency of TB infection (LTBI) with development of more severe clinical forms at relatively early stage of HIV disease when CD4 count still remains above 300/ul, makes TB a unique opportunistic infection and negatively influence the outcome of dual infection.This is suggestive of impairment of some critical immune function involving relatively less frequent fine T cell subsets with functional hierarchy over bulk T cells, so as to weaken the immune containment of LTBI resulting in reactivation of M. tuberculosis and manifestation of severe forms of TB.HIV has recently been reported to preferentially infect, destroy and incapacitate two key immune-regulatory T cell subsets, namely NKT and Treg cells.Therefore, studying them along the course of HIV disease and impact of their changes on the function of effector T cells directed against M.tuberculosis is important.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

HIV+ve+LTBI HIV+ve+clinical TB HIV-ve+clinical TB Normal control

Criteria

Inclusion Criteria:

HIV infected +LTBI group:

Patient of either sex between 18-65 years of age
All the patients should be HIV ELISA test positive irrespective of CD4 count and presence of other opportunistic infections Antiretroviral drug naive HIV patients
No past history of TB
Patients should be either tuberculin test positive (> 5mm) or interferon gamma release assay positive
Written informed consent to participate in the study given by participants or legal guardian
Patients able to comply with instructions and come back for a regular follow up

HIV infected + Clinical TB group:

Patient of either sex between 18-65 years of age
All the patients should be HIV ELISA test positive irrespective of CD4 count and presence of other opportunistic infections
In PTB group, patient should be two sputum smear positive out of three consecutive samples
In EPTB group, diagnosis of TB will be:
- Definitive -Culture confirmed
- Probable -Histopathological or radiological -Clinical features and response to anti TB treatment (ATT)
- Possible TB -Clinical feature and response to anti TB treatment (ATT)
Written informed consent to participate in the study given by participants or legal guardian
Patients able to comply with instructions and come back for a regular follow up

HIV negative Clinical TB group:

Patients of either sex between 18-65 years of age who are permanent resident of Delhi
All patients should be HIV ELISA negative
In PTB group, patients should be two sputum smear positive (at least 1+) out of three consecutive samples
In EPTB group, diagnosis of TB will be:
- Definitive -Culture-confirmed
- Probable -Histopathological or radiological -Clinical features and response to anti-TB treatment (ATT)
- Possible TB -Clinical features and response to anti-TB treatment (ATT)
Written informed consent to participate in the study given by participants or legal guardian
Patients able to comply with instructions and come back for a regular follow up

Normal controls:

Persons of either sex between 18-65 years of age who are permanent resident of Delhi
Written informed consent to participate in the study given by participants or legal guardian
Person should not have past history of TB
- Mantoux test negative (< 10mm)
- Chest-X-ray normal
- Hemogram normal
Renal and liver functions normal
Hepatitis viral markers normal
No clinical evidence of malnutrition
HIV ELISA negative

Exclusion Criteria:

HIV infected +LTBI group:

Pregnant and lactating females
Patients who are getting steroid therapy
Transplant patients, diabetes mellitus or malignancy, chronic renal failure or liver diseases
Currently receiving cytotoxic therapy, or have received it within the last 3 months
Terminally ill as per treating clinician's judgment
Patient from outside Delhi and migrants

HIV infected + Clinical TB group:

Category II and multidrug-resistant pulmonary tuberculosis
Pregnant and lactating females
Patients who are getting steroid therapy
Transplant patients, diabetes mellitus or malignancy, chronic renal failure or liver diseases
Currently receiving cytotoxic therapy, or have received it within the last 3 months
Terminally ill patient as per treating clinician's judgment
Patients from outside Delhi and migrants

HIV negative Clinical TB group:

Category II and multi drug-resistant pulmonary tuberculosis
Patients who are getting steroid therapy
Transplant patients, diabetes mellitus or malignancy, chronic renal failure or liver disease
Currently receiving cytotoxic therapy, or have received it within the last 3 months
Terminally ill patient as per treating clinician's judgment
Patients unwilling to comply with the study procedures or those with history of alcohol or drug abuse

Normal controls:

Transplant patients, diabetes mellitus or malignancy
Patients unwilling to comply with the study procedures or those with history of alcohol or drug abuse

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00692809

Contacts

Contact: Surendra K Sharma, M.D., Ph.D

26594415

surensk@gmail.com

Locations

India
All India Institute of Medical Sciences	Recruiting
New Delhi, Delhi, India, 110608
Contact: Surendra K Sharma, M.D., Ph.D 26594415 surensk@gmail.com
Contact: Sanjeev Sinha, MD 26594440 drsanjeevsinha2002@yahoo.com
Principal Investigator: Surendra K Sharma, M.D., Ph.D
Sub-Investigator: Sanjeev Sinha, MD
Principal Investigator: Dipender K Mitra, Ph.D
Sub-Investigator: Amit K Dinda, MD

Sponsors and Collaborators

Ministry of Science and Technology, India

Indian Council of Medical Research

Investigators

Principal Investigator:

Surendra K Sharma, M.D., Ph.D

All India Institute of Medical Sciences, New Delhi

More Information

No publications provided

Responsible Party:	Dr. S.K. Sharma, Professor & Head, All India Institute of Medical Sciences
ClinicalTrials.gov Identifier:	NCT00692809 History of Changes
Other Study ID Numbers:	SKS/LTBI/07
Study First Received:	June 5, 2008
Last Updated:	September 14, 2009
Health Authority:	India: Institutional Review Board

Keywords provided by Ministry of Science and Technology, India:

Latent tuberculosis infection
Human immunodeficiency virus
Tuberculosis
Natural Killer T Cells

Invariant Natural Killer T Cells
Regulatory T cells
Interferon-gamma

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Latent Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral

Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on February 09, 2012