Although current medical treatments have improved health outcomes for people living with HIV infection, for some, engagement and retention in health care and adherence to antiretroviral treatment is a challenge. In 2011, the Massachusetts Department of Public Health, Bureau of Infectious Disease and Laboratory Sciences, undertook the ‘Strategic Peer-Enhanced Care and Retention Model’ or SPECTRuM project. The project utilizes a multidisciplinary team approach including peers, nurses, and other clinical providers to enhance prompt linkage to care, intensively support retention in care, and improve adherence to prescribed treatments. This manual describes the service approaches and lessons learned from the initiative, and includes many of the assessment tools and direct care resources used throughout the project. Examples of successful interventions are provided in a variety of settings, from large, urban hospitals, to neighborhood-based community health centers. The interventions described are suitable for medical organizations, within and outside of Massachusetts. These approaches can be applied to work with diverse patient populations, including newly diagnosed individuals, hard-to-reach clients with multiple comorbidities, immigrant and refugee populations, individuals recently released from correctional facilities, persons with lower health literacy, and those with limited experience navigating the health care system.