Pleocytosis is associated with disruption of HIV compartmentalization between blood and cerebral spinal fluid viral populations

Introduction: We hypothesized that pleocytosis, which is a marker of central nervous system (CNS) inflammation, would result in viral genetic equilibration or de-compartmentalization between HIV populations in the blood and cerebrospinal fluid (CSF), suggesting viral trafficking.Methods: Study subjects, who started or interrupted their antiretroviral treatment, had viral loads measured and clonal viral env sequences generated from HIV RNA extracted from paired blood and CSF samples. White blood counts in CSF were also measured at each timepoint. Degree of inter-compartment segregation was calculated by posterior probability using linear discriminant analysis and multidimensional scaling. Co-receptor usage was determined using a trained support vector machine.Results: Pleocytosis was strongly associated with disruption of viral compartmentalization.Conclusions: Inflammation in the CNS, marked by pleocytosis, allows HIV populations to mix between blood and CSF, which may increase the overall viral genetic diversity within the CSF.