Kaposi sarcoma in the era of immunodeficiency: challenges and opportunities for treatment and prevention.

Kaposi sarcoma (KS) is a multifocal angioproliferative disorder closely linked to human herpesvirus-8 (HHV-8) infection and profound immunodeficiency. Despite landmark advances in combination antiretroviral therapy (cART) that have lowered KS incidence, this malignancy persists as a significant cause of morbidity and mortality, particularly in sub-Saharan Africa and among marginalized populations. Here, we review the current understanding of KS pathogenesis, emphasizing the interplay between viral latency, lytic reactivation, and host immune suppression. We summarize epidemiological trends before and after cART implementation, highlighting regional disparities in seroprevalence and cancer burden. Key challenges in KS management include delayed diagnosis due to lesion heterogeneity, difficulty distinguishing KS from mimickers such as bacillary angiomatosis, and barriers to histopathological confirmation in resource-limited settings. We evaluate therapeutic approaches, from early antiretroviral therapy (ART) initiation and supportive chemotherapy to novel targeted agents like pomalidomide and immune checkpoint inhibitors, and discuss their limitations and emerging prospects. Future directions focus on HHV-8 vaccine development, implementation of point-of-care diagnostics enhanced by artificial intelligence, and integration of KS surveillance into existing HIV frameworks. Comprehensive prevention strategies encompassing routine HHV-8 screening of high-risk groups, robust adherence support for ART, and interdisciplinary care models are essential to curb KS's global impact. Bridging research, clinical practice, and public health efforts will be critical to achieving equitable access to early detection and innovative treatments, thereby transforming KS from a relentless complication of HIV to a manageable condition.