Despite the substantial progress many countries in sub-Saharan Africa have made towards achieving global HIV treatment targets, retaining clients on antiretroviral therapy (ART) after treatment initiation remains a key obstacle to ending the HIV epidemic. In South Africa, disengagement from HIV care during a client’s first 12 months after initiation has recently been estimated at approximately 25%; and only 44% of clients are continuously engaged for the full 12 months, without interruptions. With current approaches to HIV service delivery failing to achieve high levels of retention in the early treatment period, new approaches to this crucial phase of care are required. Differentiated service delivery models (DSDMs) offer flexibility in terms of timing and location of access to HIV care and treatment and have the potential to overcome some of the obstacles that clients face in adhering to visit and medication schedules. Although rates of viral suppression and retention among clients enrolled in specific DSDMs have been reported, the overall effect on HIV treatment outcomes, for what is in fact a dramatic change in the way that treatment is delivered, is unclear.