This is a study that was enrolling HIV positive participants with CD4 <50 cells /mm3 and no probable or confirmed TB. The Participants were randomized at entry to receive empiric tuberculosis treatment and Efavirenz based ART or local standard of care . The participants were followed up actively at the clinic for a duration of 48 weeks and transitioned to local standard of care where there were contacted via phone calls every 3 months for another 48 weeks. The participants were in the study for a total duration on 96 weeks. Kericho site enrolled a total of 82 participants .

Study population included HIV-1 positive men and women ≥ 18 years of age with advanced HIV disease and no probable or confirmed TB as defined in the current ACTG diagnosisappendix.https://www.fstrf.org/apps/cfmx/apps/common/Portal/index.cfm?event=p ostLogin and who are initiating ART were recruited from Kericho District Hospital and nearby health facilities. There were no changes from the anticipated population. Recruitment of potential study subjects started on 28 January 2013 and the site enrolled 82 subjects (as per Jul 07, 2014). Study closed to accrual on Jul 07 2014. Total number of participants enrolled across all site are 851 out of the expected 837.

Large numbers of people have been started on antiretroviral treatment (ART) in resource-limited settings (RLS) as a result of the global commitment to universal access to ART. Tuberculosis (TB) has been shown to be the leading cause of early mortality (16-51%) in patients with advanced HIV initiating ARVs in resource limited settings including Kenya.  There are major difficulties in making a diagnosis of TB in people with severe immune deficiencies as a result of HIV infection. Currently in many RLS, TB treatment is started without microbiologic confirmation in individuals who are thought by clinicians to have active TB. TB treatment in patients without classic symptoms or signs of active TB is less likely to occur, but when implemented among individuals with very advanced HIV such treatment may improve survival. Given the difficulty in identifying active TB through current screening procedures, high incident TB and high early mortality suggests the importance and challenge of addressing TB among patients initiating ART. This is a randomized, open-label, phase IV strategy trial, carried out in resource-limited settings with main aim of comparing survival probabilities between two study arms 24 weeks after randomization. HIV-1 positive participants’ 18 years and above will be randomized to initiate TB treatment either at entry (Arm A, empiric) or isoniazid (INH) preventive treatment (IPT) and when TB treatment is indicated (Arm B, local standard of care). The Kericho site will recruit up to 100 participants who present with advanced HIV disease, no probable or confirmed TB infection and are initiating antiretroviral therapy. Recruitment will be primarily done through Kericho District Hospital HIV clinic. All enrolled participants will be followed up for 96 weeks but will be transitioned to locally provided care and treatment at week 48. The site accrual rate is estimated to be 8 participants per month; hence estimated duration of accrual is 10-12months. Given the burden of early mortality and the difficulties and time delays that are often encountered in diagnosing active TB accurately in RLS, a strategy of empiric TB therapy may be able to reduce this early mortality significantly.