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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Latent Tuberculosis Infection, HIV Infections, Tuberculosis

Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>HIV+ve+LTBI (n=100) | |
| 2<br>HIV+ve+clinical TB (n=50) | |
| 3<br>HIV-ve+clinical TB (n=15) | |
| 4<br>Normal control (n=15) | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elucidation of critical events of the cellular and molecular interactions that would be useful for developing newer therapeutic strategies and vaccination. |  | 5 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Latent tuberculosis infection, Human immunodeficiency virus, Tuberculosis, Natural Killer T Cells, Invariant Natural Killer T Cells, Regulatory T cells, Interferon-gamma