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

Condition(s) targeted: Latent Tuberculosis Infection; HIV Infections; Tuberculosis

Phase: N/A

Status: Recruiting

Sponsored by: Ministry of Science and Technology, India

Official(s) and/or principal investigator(s):
Surendra K Sharma, M.D., Ph.D, Principal Investigator, Affiliation: All India Institute of Medical Sciences, New Delhi

Overall contact:
Surendra K Sharma, M.D., Ph.D, Phone: 26594415, Email: surensk@gmail.com

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.

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

Study design: Other, Prospective

Primary outcome: 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.

Secondary outcome: Elucidation of critical events of the cellular and molecular interactions that would be useful for developing newer therapeutic strategies and vaccination.

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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

Surendra K Sharma, M.D., Ph.D, Phone: 26594415, Email: surensk@gmail.com

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

Starting date: July 2008
Ending date: March 2010
Last updated: September 14, 2009