Antiretroviral drug treatment interruption in human immunodeficiency virus-infected adults: Clinical and pathogenetic implications for the central nervous system

Abstract

Interruption of antiretroviral treatment provides a well-defined 'experimental' paradigm to study the dynamics of central nervous system (CNS) infection and host responses in relation to those of systemic infection. We review our experience with 12 subjects (9 who were viremic and three with suppressed infection at baseline) followed longitudinally with serial lumbar punctures and neurological evaluations after stopping their antiretroviral treatments. All but two subjects exhibited an increase in cerebrospinal fluid (CSF) HIV RNA. Approximately half of the cohort developed a substantial, though asymptomatic, CSF lymphocytic pleocytosis with CSF counts rising to 30-60 cells/microL in five of the subjects. Subjects with higher CSF cell counts exhibited higher CSF HIV concentrations. We interpret the relationship of CSF HIV concentrations and pleocytosis in the context of a simple model of virus and cell exchange between blood and CSF. The proportionally greater increase in CSF HIV after treatment interruption indicates that CSF HIV infection is often more effectively suppressed by combination antiretroviral therapy than is systemic infection.