BACKGROUND: Health inequality in Latin America is particularly severe for individuals living with HIV (PLHIV) and key populations, such as men who have sex with men, transgender women, people who use drugs, and sex workers. Despite regional programs aimed at reducing health inequalities, such as the Sustainable Development Goals and the Sustainable Health Agenda for the Americas 2018-2030, the COVID-19 health crisis has exposed significant shortcomings in national healthcare systems for PLHIV and key populations. The multi-country, community-based research program, EPIC, was developed by Coalition PLUS within an network of community-based organizations engaged in the response to HIV and viral hepatitis. The EPIC program aimed to study the impact of the COVID-19 health crisis on 1) key populations (KP) and/or PLHIV or hepatitis C
2) community health workers (CHWs) and peer educators
and 3) key innovations and adaptations in HIV/HCV services. The objective of this article is to highlight main issues faced in the region during the COVID-19 health crisis in order to inform national and international policies. METHODS: A general protocol and study materials were developed and included built-in flexibility to allow participating organizations to adapt the study to local needs in terms of target populations and specific areas of interest. Data were collected through surveys and/or interviews. In total 118 studies were conducted across 31 countries: 66 quantitative (n = 12,060 among KP or PLHIV or people living with HCV and n = 811 among CHWs) and 52 qualitative (n = 766 among KP or PLHIV or people living with HCV and n = 136 among CHWs). DISCUSSION: Findings in Latin America highlight the difficulties faced by PLHIV and KP in accessing health services, as well as issues of discrimination, violence, and mental health challenges, all of which have been exacerbated by the health crisis. Additionally, the study highlights strategies implemented by community CHWs and peer educators to mitigate the negative impact of the crisis. Moreover, EPIC demonstrates the ability of community agents to generate scientific evidence that raises public awareness of the situation faced by the most vulnerable populations. CONCLUSION: National and international policies must recognize and support the unique capacity of CHWs and peer educators to adapt health interventions to the specific needs of communities. Policymakers are also urged to involve the community in the development of public policies aimed at reducing inequalities and improving the living conditions of vulnerable populations.