Tuberculosis (TB) is a major public health problem in the world and is the leading AIDS related opportunistic infection (infection that is normally mild in a healthy person, but takes advantage of an ill person's weakened immune system to move into the body, multiply, spread, and cause serious illness) hence the need to prevent active TB by treating latent TB. Kenya is one of the 22 high TB burden countries in the world which collectively contribute 80% of the global TB disease burden. Some people are infected with the bacteria that cause TB, but their immune systems (the system in a person’s body that helps fight infections) prevent the bacteria from multiplying and they do not have any symptoms from the infection; these people are said to have latent TB infection. Latent TB can develop into active disease and cause sickness, especially in people with weakened immune systems, such as those with HIV. The standard way to keep latent TB from becoming active is treatment with 6 to 9 months of daily isoniazid, an anti-TB drug. In Kenya the standard treatment is use of isoniazid for 6 months. This has been associated with high proportion of individuals who fail to complete even 6 months of isoniazid preventive therapy. This highlights the need for alternative, more effective short-course approaches for treatment of Latent Tuberculosis infection. This study will compare a 4 week daily rifapentine/isoniazid regimen to a standard 9 month daily isoniazid regimen for the prevention of TB in HIV infected participants without evidence of active TB. The primary objective will be efficacy of TB prevention. HIV infected participants of ≥18years will be randomly assigned to receive either  rifapentine/isoniazid for 4 weeks daily or isoniazid  for 36 weeks daily. The Kericho site will recruit about 150 participants. Recruitment will be done from Kericho District Hospital HIV clinic and nearby health facilities. All enrolled participants will be followed up for 156 weeks after the last participant is enrolled. If ultra short course drug treatment of rifapentine/isoniazid is not inferior than standard 9 months isoniazid in prevention of active TB, this information will be shared with the Ministry of Health who will help in making policies on the appropriate use of the new regimen in prevention of active TB.

Tuberculosis (TB) is a major public health problem in the world and is the leading AIDS related opportunistic infection. 2009World Health Organization (WHO) data collection estimated that there were 9.4 million new incident cases of tuberculosis. Among new incident cases of TB, 1.1million (11%) were HIV co-infected and 35% of TB deaths were among HIV co-infected individuals. Kenya is one of the 22 high TB burden countries in the world which collectively contribute 80% of the global TB disease burden. In Kenya, 106,083 cases of TB were reported in the year 2010. HIV infection contributes significantly to an increased risk of progression of Latent TB infection (LTBI) to active TB. Isoniazid taken for 6-9 months has been the cornerstone of treatment for LTBI to prevent active TB for more than 30 years though this has been associated with high proportion of individuals who fail to complete even 6 months of isoniazid preventive therapy. This highlights the need for alternative, more effective short-course approaches for treatment of LTBI. This study will compare a 4 week daily rifapentine/isoniazid regimen to a standard 9 month daily isoniazid regimen for the prevention of TB in HIV infected participants without evidence of active TB. The primary objective will be efficacy of TB prevention. HIV infected participants of ≥18years will be randomized to receive either  rifapentine/isoniazid for 4 weeks daily or isoniazid  for 36 weeks daily. Safety and tolerability of the regimens, adherence to treatments and patterns of antibiotic resistance among Mycobacterium tuberculosis isolates in participants who fail on these prophylactic regimens will be assessed. The Kericho site will recruit about 100 participants. Recruitment will be done from Kericho District Hospital HIV clinic and nearby health facilities. All enrolled participants will be followed up for 156 weeks after the last participant is enrolled. The site accrual rate is estimated to be 6 participants per month; hence estimated duration of accrual is about 2years.If ultra short course rifapentine/isoniazid is more efficacious than standard 9 months isoniazid, this information will be passed to the Ministry of Health which will help in making policies on the appropriate use of the new regimen in various TB control