• Rate of microbiologically confirmed TB or highly probable TB during the 36 month risk period
  

• Rate of drug toxicity during and the end of the 36 month risk period
  
• Proportions adhering to study drug and HAART at the end of each study year
  
• Mortality rate during and at the end of the 36 month risk period
  
• Rate of development of INH monoresistance during and at the end of the 36 month risk period.
  

The incidence of Tuberculosis (TB) in poor settlements around Cape Town continues to rise despite highly-active-anti-retroviral therapy (HAART) roll-out and DOTS. In Khayelitsha district, where this project will be conducted, TB incidence is about 1600/100000. There is an equally high HIV prevalence, currently 33%. Over 50% of adults presenting with active TB are co-infected with HIV and a third of all patients starting HAART have active TB. Although HAART has been shown to reduce the overall risk of TB by 59-80%, this risk still far exceeds the general risk. In the Khayelitsha HAART cohort, the risk of developing TB whilst on HAART is ~12 per 100 p-y. In the nearby community of Gugulethu, there is a 14% risk of active TB with at least half of the cases occurring within the first 3months on HAART. In a region where RD1-detected prevalence of latent TB infection is at least 80%, there is a real concern that TB will likely undo the benefit of HAART in the long run. Additional measures are therefore required to reduce the risk of TB in those already receiving or starting HAART. Isoniazid preventive therapy (IPT) represents an option but there is insufficient evidence to determine whether IPT can further (and safely) reduce the risk of TB in the HAART era. In a RCT, we propose to evaluate whether IPT can reduce the risk of active TB in patients receiving HAART. This study requires a minimum person years of follow-up of 3816 in total to detect a 30% difference or more in the overall rate of tuberculosis between the intervention and control group, λ1= 0.052 per year and λ0=0.085 per year at 80% power and 5% significance level. Participants will be observed at risk for a total of 36 months. Development of microbiologically confirmed will be the primary endpoint.