HAND in Africa: prevalence, diagnostic challenges and the search for objective markers.

HIV Associated Neurocognitive Disorder (HAND) affects 20-50% of people with HIV (PWH) on suppressive antiretroviral therapy, with about 72% of the 16 million global cases residing in sub-Saharan Africa. Despite this disproportionate burden, HAND remains very challenging to diagnose. The Frascati diagnostic criteria which are considered the mostly used criteria albeit with recent challenges require specialist to administer the neuropsychological batteries, making it inaccessible, literacy-dependent, and culturally biased in resource-limited African settings. This creates a significant diagnostic capacity gap. Identifying and developing biomarker-based HAND diagnostic assays are critical to the early detection and effective management of HAND among people with HIV in Africa and other resource-limited settings. This narrative review used 80 articles to critically evaluate HAND neuropathogenesis, existing diagnostic tools, and the emerging peripheral blood biomarker landscape. HIV establishes a persistent CNS reservoir that drives neuroinflammation through infected microglia, dysfunctional activation of astrocytes, and neurotoxic viral proteins mainly gp120, and Tat, independently of immune-virologic state of the PWH. Among candidate biomarkers, serum ICAM-5, serum ATP, and plasma neurofilament light chain (NfL) appear to be among the most promising candidates; validating such markers in a multicenter approach to complement Africa friendly neuro-psychological test tools will help improve on HAND diagnosis. Once some biomarkers are validated, we propose that a 3-tier multi-marker diagnostic framework that could be used in complementing validated tools, spanning primary care serum-based screening through to specialist CSF biomarker profiling could enable objective, regional friendly, and early HAND detection at the point of HIV care across Africa.