Immune checkpoint inhibitors for African people living with HIV: T-cell exhaustion, endemic co-infections, and the oncology trial gap

Immune checkpoint inhibitors (ICIs) have fundamentally transformed modern oncology by unleashing the body’s anti-tumor immunity, yet people living with HIV (PLWH) were systematically excluded from the pivotal registration trials. This evidence gap is especially consequential in sub-Saharan Africa, a region that bears 67% of the global HIV burden alongside an escalating, complex cancer epidemic. Chronic HIV infection is characterized by progressive T-cell exhaustion driven by sustained upregulation of inhibitory receptors such as PD-1, TIGIT, LAG-3, and TIM-3 on HIV-specific T cells. While this profound exhaustion provides a strong mechanistic rationale for checkpoint blockade to restore immune function and clear infected cells, the African communities most in need of these therapies face the steepest barriers to receiving them. To address this critical disparity, this state-of-the-art review synthesizes current evidence from recent peer-reviewed publications, clinical trial registries, and regional health assessments. Current clinical evidence demonstrates that ICIs can be safely and effectively administered to virologically suppressed PLWH with adequate CD4 + counts, yielding cancer response rates comparable to HIV-negative cohorts. In PD-1 inhibitor–naïve Kaposi sarcoma, objective response rates exceeding 80% have been reported; Similarly encouraging safety and response data have emerged in HIV-positive patients with lung cancer, where PD-1 inhibitors produce outcomes broadly comparable to those in HIV-negative populations. However, the immunological landscape in Africa is uniquely complicated by endemic co-infections, which promote an immunosuppressive Th2-biased environment that may alter checkpoint expression, ICI responsiveness, and toxicity profiles. Most concerningly, sub-Saharan Africa remains almost entirely excluded from ICI clinical trials due to acute workforce shortages, infrastructure gaps, and prohibitive costs. Extending the benefits of immunotherapy to this population is an ethical imperative that requires pragmatic, African-led trial designs, routine helminth screening, sustainable capacity-building, and equitable global partnerships.