Distinct from HIV-1 and often neglected in the global campaign to end the AIDS epidemic, HIV-2 presents unique and underappreciated challenges in diagnosis, clinical care, antiretroviral therapy (ART), and HIV programmatic management. Here, we review the epidemiology and natural history of HIV-2, diagnostics and algorithms for accurately diagnosing and differentiating HIV-2 from HIV-1, the unique features of HIV-2 ART and drug resistance, and the clinical care and management of patients infected with HIV-2 in both developed and resource-limited settings. Ultimately, further research is needed to address the gaps in our knowledge of HIV-2 infection, increased resources are needed to specifically target HIV-2 as part of the UNAIDS/WHO 90-90-90 campaign to end AIDS, and increased determination is needed to better advocate for inclusion of people living with HIV-2 in global HIV/AIDS initiatives.
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