A major challenge to successful implementation of both antiretroviral and anti-tuberculosis therapy in low-resource settings remains the ability to diagnose and monitor the progress of both infections, a process that is hampered by lack of laboratory infrastructure, technical skill and poor integration of HIV and TB services. Recent technological innovations in the Point of Care (POC) testing arena promises to alleviate the problem by providing access to on-site laboratory tests with the future potential of integrating testing platforms. To date, little attention has been paid to the difficulties which are likely to arise during large scale multi-disciplinary POC implementation programs, particularly in high-burden disease prevalence settings. The primary objective of this randomized controlled trial is to compare the effectiveness, timeliness, and costs of using a POC laboratory compared to using the Standard of Care (a centralized laboratory) for ART initiation in South Africa in ‘real-world’ conditions, in order to make policy recommendations about the use of POC technology. The study is being led by the National Health Laboratory Service (NHLS) with HE2RO carrying out the costing of the trial and ascertaining epidemiologic outcomes.