HIV-1 Infection of the Central Nervous System, Its Consequences and Treatment

Dear Colleagues,

Exposure of the central nervous system (CNS) to HIV-1 occurs early during primary infection, and thereafter viral RNA is readily detected in the cerebrospinal fluid (CSF) of nearly all untreated viremic individuals. Additionally, the character of infection changes as systemic infection and disease progress: There is both continued viral re-exposure from the blood and independent selection and viral evolution within the CNS that leads to ‘compart­mentalized’ CNS HIV-1 populations diverging genetically and phenotypically from those of blood. The clinical consequences of CNS HIV-1 infection also change, from early, very common but largely asymptomatic, meningeal inflammation to late, and less common, ‘invasive’ HIV-1 encephalitis with important neurological deficits. Combination antiretroviral therapy (ART) is largely effective in suppressing HIV-1 RNA within the CSF and preventing more severe CNS disease, but not entirely. Rare patients exhibit neurosymptomatic CNS escape related to virological treatment failure within the CNS despite effective plasma HIV-1 RNA suppression. More commonly, some individuals exhibit neurocognitive dysfunction despite apparent control of viral RNA in both blood and CSF. Moreover, the CNS may provide a reservoir site for persistence of HIV-infected cells and a potential impediment to HIV-1 cure efforts.

This Special Issue of Viruses focuses on the pathobiology of CNS HIV-1 infection, particularly on its epidemiology, genetic and phenotypic evolution, molecular and cellular pathogenesis, and treatment implications. It draws directly on human HIV-1 studies but also on animal models of CNS lentivirus infections. It will assemble a broad collection of reviews and research papers that together provide a comprehensive and provocative view of this important facet of HIV-1 infection. This state-of-the-art summary will provide a foundation for future studies to further explore CNS infection and its clinical manifestations to develop more effective prevention and mitigation approaches, and to eventually serve as a basis for cure strategies directed at the CNS viral reservoir.

Prof. Richard W. Price
Prof. Ronald Swanstrom
Prof. Magnus Gisslen
Guest editors

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• HIV
• central nervous system (CNS)
• cerebrospinal fluid (CNS)
• antiretroviral therapy (ART)
• tropism
• neurocognitive impairment
• compartmentalization