Potential for early antiretroviral therapy to reduce central nervous system HIV-1 persistence

: Although treatment with antiretroviral therapy (ART) improves central nervous inflammation, limits viral replication detected in the cerebrospinal fluid, and prevents severe clinical neurological disease in most individuals, HIV-1 can persist in the central nervous system (CNS) despite ART. Recent observations that initiation of ART early in the course of infection limits the size of systemic HIV reservoirs, parallel clinical reports of increased rates of posttreatment viral control in early treatment cohorts, and an understanding of the dynamics of HIV-1 infection and neuropathogenesis during early infection provides rationale to consider that ART started early in the course of HIV-1 infection may have a beneficial effect on CNS HIV-1 persistence. Early ART may restrict the initial establishment of HIV-1 infection in cells of the CNS, and furthermore, may reduce levels of immune activation and inflammation that allow perpetuation of CNS infection. In this review, we consider the precedent set by studies of the impact of early treatment on systemic HIV-1 reservoirs, summarize the current understanding of early CNS HIV-1 exposure and its effects, and examine the evidence for a benefit in the CNS compartment of early treatment.