OBJECTIVE: To determine whether a multiple-dose series of an inactivated whole cell mycobacterial vaccine, Mycobacterium vaccae, can prevent HIV-associated tuberculosis. DESIGN AND METHODS: The DarDar trial was a randomized, placebo-controlled, double-blind trial. The study was carried in an outpatient facility in Dar es Salaam, Tanzania. HIV-infected patients with CD4 cell counts of at least 200 cells/microl and a Bacille Calmette-Guérin scar were chosen for the study. The intervention was carried out by random 1:1 assignment to five intradermal doses of M. vaccae or placebo. Tuberculin skin tests were performed, and patients with reactions of at least 5 mm were administered isoniazid for 6 months. The main outcome measures were disseminated (primary endpoint), definite, and probable tuberculosis (secondary endpoints). RESULTS:Two thousand thirteen individuals were randomized (1006 to M. vaccae, 1007 toplacebo) and followed every 3 months for a median of 3.3 years. The trial was terminated early because of slow accrual of cases of disseminated tuberculosis and significant protection against definite tuberculosis. Hazard ratios were disseminated tuberculosis 0.52 (95% confidence interval 0.21-1.34; seven cases in M. vaccae, 13 cases in placebo; log-rank P = 0.16), definite tuberculosis 0.61 (95% confidence interval 0.39-0.96; 33 cases in M. vaccae, 52 cases in placebo; P = 0.03), and probable tuberculosis 1.17 (95% confidence interval 0.76-1.80; 48 cases in M. vaccae, 40 cases in placebo; P = 0.46). Immunization was well tolerated, with no adverse effect on CD4 cell count or HIV viral load, and no increase in the rate of serious adverse events. CONCLUSION: Administration of a multiple-dose series of M. vaccae to HIV-infected adults with childhood Bacille Calmette-Guérin immunization is safe and is associated with significant protection against definite tuberculosis. These results provide evidence that immunization with a whole cell mycobacterial vaccine is a viable strategy for the prevention of HIV-associated tuberculosis.
RCT Entities:
OBJECTIVE: To determine whether a multiple-dose series of an inactivated whole cell mycobacterial vaccine, Mycobacterium vaccae, can prevent HIV-associated tuberculosis. DESIGN AND METHODS: The DarDar trial was a randomized, placebo-controlled, double-blind trial. The study was carried in an outpatient facility in Dar es Salaam, Tanzania. HIV-infectedpatients with CD4 cell counts of at least 200 cells/microl and a Bacille Calmette-Guérin scar were chosen for the study. The intervention was carried out by random 1:1 assignment to five intradermal doses of M. vaccae or placebo. Tuberculin skin tests were performed, and patients with reactions of at least 5 mm were administered isoniazid for 6 months. The main outcome measures were disseminated (primary endpoint), definite, and probable tuberculosis (secondary endpoints). RESULTS: Two thousand thirteen individuals were randomized (1006 to M. vaccae, 1007 to placebo) and followed every 3 months for a median of 3.3 years. The trial was terminated early because of slow accrual of cases of disseminated tuberculosis and significant protection against definite tuberculosis. Hazard ratios were disseminated tuberculosis 0.52 (95% confidence interval 0.21-1.34; seven cases in M. vaccae, 13 cases in placebo; log-rank P = 0.16), definite tuberculosis 0.61 (95% confidence interval 0.39-0.96; 33 cases in M. vaccae, 52 cases in placebo; P = 0.03), and probable tuberculosis 1.17 (95% confidence interval 0.76-1.80; 48 cases in M. vaccae, 40 cases in placebo; P = 0.46). Immunization was well tolerated, with no adverse effect on CD4 cell count or HIV viral load, and no increase in the rate of serious adverse events. CONCLUSION: Administration of a multiple-dose series of M. vaccae to HIV-infected adults with childhood Bacille Calmette-Guérin immunization is safe and is associated with significant protection against definite tuberculosis. These results provide evidence that immunization with a whole cell mycobacterial vaccine is a viable strategy for the prevention of HIV-associated tuberculosis.
Authors: Timothy Lahey; Robert D Arbeit; Muhammad Bakari; C Robert Horsburgh; Mecky Matee; Richard Waddell; Lillian Mtei; Jenni M Vuola; Kisali Pallangyo; C Fordham von Reyn Journal: Vaccine Date: 2010-09-25 Impact factor: 3.641
Authors: Lisa V Adams; Barry N Kreiswirth; Robert D Arbeit; Hanna Soini; Lillian Mtei; Mecky Matee; Muhammad Bakari; Timothy Lahey; Wendy Wieland-Alter; Elena Shashkina; Natalia Kurepina; Jeffrey R Driscoll; Kisali Pallangyo; C Robert Horsburgh; C Fordham von Reyn Journal: J Clin Microbiol Date: 2012-05-30 Impact factor: 5.948
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Authors: Yuri V Efremenko; Dmytro A Butov; Natalia D Prihoda; Svetlana I Zaitzeva; Larisa V Yurchenko; Nina I Sokolenko; Tetyana S Butova; Anna L Stepanenko; Galyna A Kutsyna; Vichai Jirathitikal; Aldar S Bourinbaiar Journal: Hum Vaccin Immunother Date: 2013-06-19 Impact factor: 3.452
Authors: Mark Hatherill; Hendrik Geldenhuys; Bernadette Pienaar; Sara Suliman; Phalkun Chheng; Sara M Debanne; Daniel F Hoft; W Henry Boom; Willem A Hanekom; John L Johnson Journal: Vaccine Date: 2014-05-09 Impact factor: 3.641
Authors: Conrad Kabali; Lillian Mtei; Daniel R Brooks; Richard Waddell; Muhammad Bakari; Mecky Matee; Robert D Arbeit; Kisali Pallangyo; C Fordham von Reyn; C Robert Horsburgh Journal: Tuberculosis (Edinb) Date: 2013-03-22 Impact factor: 3.131