From epidemiology to phenotyping: Characterizing neurologic dysfunction in Sub-Saharan Africans with HIV

Background Neurological complications remain an important manifestation of HIV infection, particularly as advances in diagnosis and antiretroviral therapy have increased survival. Despite this, neurological research in sub-Saharan Africa has remained largely focused on describing the epidemiology of established disease, with limited emphasis on systematically characterizing neurological dysfunction. Perspective For populations in sub-Saharan Africa, we advocate for a shift from predominantly epidemiological descriptions of HIV-associated neurological disease towards systematic, multidimensional phenotyping of neurological dysfunction. Neurological involvement extends beyond HIV-associated neurocognitive disorders (HAND) to include central, peripheral, and autonomic nervous system dysfunction, including subclinical abnormalities that may not be detected through routine clinical assessment. Neurological phenotyping integrates clinical and behavioral assessments, structural and functional neuroimaging, neurophysiological profiling, molecular and multi-omic approaches, and digital phenotyping to characterize dysfunction across a spectrum from subclinical abnormalities to clinically overt disease. These approaches can improve understanding of disease biology, identify population-specific phenotypes and biomarkers, and enhance risk stratification and prognostication. Challenges and opportunities Sub-Saharan African populations remain underrepresented in neurological phenotyping research, limiting the generalizability of existing phenotypes and biomarkers. The continent's substantial genetic diversity, high burden of neurotropic infections, and diverse sociocultural and linguistic contexts further underscore the need for locally generated evidence. Importantly, many phenotyping approaches can be implemented within existing hospitals, universities, and academic medical centers through strategic investment, capacity building, research networks, and external funding. Conclusion Greater African ownership of neurological research, supported by equitable international partnerships, could accelerate the transition from describing the burden of HIV-associated neurological disease to systematically characterizing its phenotypes, providing a foundation for more precise prevention, diagnosis, prognostication, and treatment.