Current treatment approaches cannot predict, ensure, or sustain the needed adherence required to achieve long-term successful therapy in many of our urban poor patients. The current treatment paradigm in the United States thus relies heavily on sequential therapy to maintain patient health. This approach is often unsuccessful in achieving viral durable suppression, increases the complexities of care, increases the costs of care, and can fail to improve patients' health. As the HIV epidemic shifts into the urban poor in the USA, the success of the current antiretroviral therapy approach to achieve durable viral suppression in this population remains under question. New treatment delivery programmes designed to address these concerns for the urban poor in the USA may represent models that can achieve high levels of treatment success in resource-limited countries.