Investigational Vaccine for the Prevention of Disseminated Tuberculosis in HIV Infected People

Study Overview
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Brief Summary
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A significant number of HIV infected patients in Africa also have disseminated tuberculosis (infection throughout multiple organs). This type of tuberculosis is a significant cause of mortality in these patients. The purpose of this study is to evaluate the safety and effectiveness of a vaccine designed to prevent disseminated tuberculosis.

Detailed Description
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Disseminated infection with Mycobacterium tuberculosis (dMTB) has been documented in 10% to 25% of patients with HIV infection in Africa. Unlike pulmonary tuberculosis (pMTB), most cases of dMTB are not recognized and death ensues rapidly. Therefore, dMTB may be a more important cause of HIV-associated mortality than pMTB in developing countries. Mycobacterium vaccae (MV) is an investigational vaccine prepared by heat inactivation of a nontuberculous mycobacteria. MV immunization may reduce the risk of HIV-associated dMTB. The purpose of this study is to define risk factors for HIV-associated dMTB and to assess the safety and effectiveness of an MV vaccine for the prevention of HIV-associated pulmonary and disseminated tuberculosis. HIV positive patients with prior BCG immunization and HIV negative controls will be entered in a 5-year study in Tanzania. Participants will be randomized to receive a 5-dose series of MV or placebo over 12 months, with a repeat skin test at Month 14. Baseline evaluation will include medical history, chest x-ray, skin tests with purified protein derivative (PPD), and blood tests to evaluate interferon-gamma production. Participants with PPD reactions greater than or equal to 5 mm will receive 6 months of prophylaxis with isoniazid. Participants will be followed every 3 months for 3 to 5 years to assess new pMTB (microbiologic or clinical diagnosis) or dMTB (microbiologic diagnosis). Potential risk factors for dMTB will also be assessed.

Official Title
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DARDAR Health Project (Disseminated Tuberculosis and HIV Infection)

Conditions
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Tuberculosis, HIV Infections

Intervention / Treatment
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* Biological: SRL-172


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infection CD4 count more than 200 cells/mm3 BCG scar Exclusion Criteria: Active tuberculosis. Patients will be deferred from study enrollment until they show no signs of active disease. Serious underlying disease (e.g., congestive heart failure, advanced cancer) Life expectancy of less than 2 years Pregnancy. Women who are pregnant may be eligible for the study after they give birth.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: B<br> | Biological: SRL-172<br>* 5 doses of 0.1mL vaccine or placebo given intradermally over 12-months<br>|
| Experimental: A<br> | Biological: SRL-172<br>* 5 doses of 0.1mL vaccine or placebo given intradermally over 12-months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and efficacy of a prime-boost immunization strategy for the prevention of HIV-associated dTB and pTB |  | every six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk factors for HIV-associated dTB and relative contributions of primary infection, reinfection, and reactivation in its pathogenesis |  | every six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCG, Mycobacterium vaccae, Disseminated tuberculosis, SRL-172, DAR-901