• 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

• Mtei L, Matee M, Herfort O, Bakari M, Horsburgh CR, Waddell R, Cole BF, Vuola JM, Tvaroha S, Kreiswirth B, Pallangyo K, von Reyn CF. High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in Tanzania. Clin Infect Dis. 2005 May 15;40(10):1500-7. Epub 2005 Apr 12.
• Lahey T, Matee M, Mtei L, Bakari M, Pallangyo K, von Reyn CF. Lymphocyte proliferation to mycobacterial antigens is detectable across a spectrum of HIV-associated tuberculosis. BMC Infect Dis. 2009 Feb 23;9:21.
• Munseri PJ, Talbot EA, Mtei L, Fordham von Reyn C. Completion of isoniazid preventive therapy among HIV-infected patients in Tanzania. Int J Tuberc Lung Dis. 2008 Sep;12(9):1037-41.

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.