About 2 billion people globally are latently infected with Mycobacterium Tuberculosis (MTB), the bacterium that causes tuberculosis (TB) disease. 8.6 million Incident cases of MTB were reported in 2012 by the world health organization, (WHO). TB is the most common opportunistic infection and the leading cause of death in adults infected with the human immunodeficiency virus (HIV), especially in Africa, where rates of TB have risen sharply over the last two decades. The lifetime risk of developing TB disease after infection is between 5-10 percent, with the highest risk within the first 2 years after infection. In people with HIV, the risk of developing TB disease is approximately 10% per year in people with latent TB infection. Treatment of latent TB amongst people living with HIV (PLWHIV) is of paramount public health importance as it would reduce the number of people carrying the bacilli and therefore reduce morbidity and mortality as well as reduce the spread of TB.  Currently the treatment of latent TB infection LTBI, involves daily administration of INH for 9 months. Shorter regimens may increase adherence and may reduce drug toxicity, both of which would be welcome developments in treatment of LTBI. This proposal will compare two treatment regimens with the primary objective being the efficacy of TB prevention. The first regimen will be the standard regimen of INH given daily for 9 months. The comparison regimen will be an ultra-short course treatment where INH will be given daily with Rifapentine for 4 weeks. The proposal will look at the efficacy of prevention along with safety and tolerability, and resistance patterns in patients who develop TB in spite of the prophylactic regimens.