Melanoma in People Living with HIV: Immune Landscape Dynamics and the Role of Immuno- and Antiviral Therapies

The intersection of HIV and melanoma presents a complex and unique challenge, marked by distinct patterns in incidence, mortality, and treatment response. Higher mortality rates among people with HIV who develop melanoma underscore an urgent need to identify the factors influencing these outcomes. Investigating immune system dynamics, the effects of anti-retroviral drugs, and the evolving landscape of cancer immunotherapy in this population holds promise for new insights, though significant uncertainties remain. Over the past 25 years, melanoma research has demonstrated that a robust immune response is critical for effective treatment. In the context of chronic HIV infection, viral reservoirs enable the virus to persist despite anti-retroviral therapy and foster dysregulated myeloid and T cell compartments. The resulting chronic inflammation weakens the immune system and damages tissues, potentially creating "cold" tumor microenvironments that are less responsive to therapy. In this challenging context, animal models become invaluable for uncovering underlying biological mechanisms. While these models do not fully replicate human HIV infection, they provide essential insights into critical questions and inform the development of tailored treatments for this patient population. Clinically, increasing trial participation and creating a centralized, accessible repository for HIV and cancer samples and data are vital. Achieving these goals requires institutions to address barriers to research participation among people with HIV, focusing on patient-centered initiatives that leverage biomedical research to improve their outcomes and extend their lives.