UC San Diego

HIV-1 associated neurocognitive disorders (HAND) remain a significant problem worldwide and can range in severity from disabling dementia to asymptomatic cognitive, motor and behavioral changes. Clinical assessments are the gold standard for detecting impairment and have defined the scope and severity of HAND; however, the viral determinants of HAND are not well understood. To further characterize the viral determinants of HAND, we studied viral evolution and disease by analyzing HIV-1 RNA extracted from blood and CSF samples along with participant specific clinical and neuropsychological assessments. HIV-1 RNA was amplified with Polymerase Chain Reaction (PCR) and sequenced using the Sanger Method. Neuropsychological assessments were administered and scored by trained psychometrists and included seven ability domains: learning, delayed recall, verbal fluency, processing speed, attention/working memory, abstraction/ executive functioning and motor speed. HIV-1 population diversity was positively associated with disease, specifically AIDS and neuropsychological impairment. Further, antiretroviral resistance was associated with lower CSF viral loads and with better neuropsychological performance. Our findings suggest that HIV-1 virulence is most likely associated with the capacity of a viral population to maintain genetic diversity and not simply a specific and predominant genotypic variant. Although, the exact underlying mechanism for this remains unclear, complex phenotypes such as neuropsychological impairment may result from different HIV-1 variants operating in a coordinated manner to cause disease