Daily Isoniazid to Prevent Tuberculosis in Infants Born to Mothers With HIV
Summary
Tuberculosis (TB) is highly endemic in sub-Saharan Africa. The increased burden of TB in settings with high prevalence of the Human Immunodeficiency Virus (HIV) is associated with high rates of transmission of Mycobacterium tuberculosis (M.tb) to both adults and children. Children infected with TB have a higher risk of developing severe disease than adults with TB. The purpose of this study was to determine if the antibiotic isoniazid (INH) prevented TB infection in infants born to HIV-infected mothers.
Timeline
- Start
- 2004-02
- Primary completion
- 2009-05
- Completion
- 2009-05
Outcome
Missed primary endpoint
Stopped: “Data Safety Monitoring Board (DSMB) recommended stopping study due to futility”
registry HIVpos/INH vs HIVpos/PL; p = 0.93; Hazard Ratio (HR) 0.98 (95% CI 0.67 to 1.44) NCT00080119 ↗
registry HIVneg/INH vs HIVneg/PL; p = 0.43; Hazard Ratio (HR) 0.85 (95% CI 0.55 to 1.30) NCT00080119 ↗
paper Primary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine. PMID 21732834 ↗
Publications
- Background Chintu C, Mwaba P. Tuberculosis in children with human immunodeficiency virus infection. Int J Tuberc Lung Dis. 2005 May;9(5):477-84.
- Background Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, Dye C. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med. 2003 May 12;163(9):1009-21. doi: 10.1001/archinte.163.9.1009.
- Background de Jong BC, Israelski DM, Corbett EL, Small PM. Clinical management of tuberculosis in the context of HIV infection. Annu Rev Med. 2004;55:283-301. doi: 10.1146/annurev.med.55.091902.103753.
- Background Toossi Z. Virological and immunological impact of tuberculosis on human immunodeficiency virus type 1 disease. J Infect Dis. 2003 Oct 15;188(8):1146-55. doi: 10.1086/378676. Epub 2003 Sep 30.
- Results Cotton MF, Schaaf HS, Lottering G, Weber HL, Coetzee J, Nachman S; PACTG 1041 Team. Tuberculosis exposure in HIV-exposed infants in a high-prevalence setting. Int J Tuberc Lung Dis. 2008 Feb;12(2):225-7.
- Results Cotton M, Kim S, Rabie H, Coetzee J, Nachman S. A window into a public program for prevention of mother to child transmission of HIV: evidence from a prospective clinical trial. South Afr J HIV Med. 2009 Jan 1;10(4):16-19. doi: 10.4102/sajhivmed.v10i4.257.
- Gupta A, Montepiedra G, Gupte A, Zeldow B, Jubulis J, Detrick B, Violari A, Madhi S, Bobat R, Cotton M, Mitchell C, Spector S; IMPAACT NWCS113 and P1041 Study Team. Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants. PLoS One. 2016 Feb 12;11(2):e0148649. doi: 10.1371/journal.pone.0148649. eCollection 2016.
- Madhi SA, Nachman S, Violari A, Kim S, Cotton MF, Bobat R, Jean-Philippe P, McSherry G, Mitchell C; P1041 Study Team. Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children. N Engl J Med. 2011 Jul 7;365(1):21-31. doi: 10.1056/NEJMoa1011214.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Isoniazid | Small molecule | 10 mg/kg | Oral |
| Subject | Isoniazid | Small molecule | 20 mg/kg | Oral |
| Background | Trimethoprim/Sulfamethoxazole | Unknown | 5 mg/kg | Oral |