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

• safety and efficacy of a prime-boost immunization strategy for the prevention of HIV-associated dTB and pTB
• Risk factors for HIV-associated dTB and relative contributions of primary infection, reinfection, and reactivation in its pathogenesis

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.

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.

• Tuberculosis
• HIV Infections

• Placebo Comparator: B
  Intervention: Biological: Mycobacterium vaccae
• Experimental: A
  Intervention: Biological: Mycobacterium vaccae

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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.