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

Sponsor

Ministry of Science and Technology, India (Other)

Overall Status

Unknown status

CT.gov ID

NCT00692809

Collaborator

Indian Council of Medical Research (Other)

180

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Latent Tuberculosis Infection HIV Infections Tuberculosis

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

180 participants

Time Perspective:

Prospective

Official Title:

Impact of HIV Infection on Latent TB Among Patients With HIV-TB Co-infection

Study Start Date :

Jul 1, 2008

Anticipated Primary Completion Date :

Mar 1, 2010

Anticipated Study Completion Date :

Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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)

Outcome Measures

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. [5 months]

Secondary Outcome Measures

Elucidation of critical events of the cellular and molecular interactions that would be useful for developing newer therapeutic strategies and vaccination. [5 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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