The brain is a major target for HIV infection and is a potential viral reservoir even in virologically well-controlled HIV-infected individuals. Data presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) suggested that during early HIV infection, CD4+ T cells in the meninges and choroid plexus serve as an important early site of HIV infection in the central nervous system (CNS), with brain macrophages and microglial cells becoming an important source of viral replication with advancing disease. Longitudinal evaluations of HIV-associated neurocognitive disorder (HAND) demonstrated that cognitive changes occur during early HIV infection and may remain during chronic infection despite virologic control by antiretroviral therapy. Cerebrospinal fluid escape during treatment was noted in numerous cohorts and pathogenetically evaluated as a state of persistent CNS HIV infection despite antiretroviral therapy. Non-HIV risk factors identified for cognitive impairment were depression and frailty. Questions remain concerning appropriate cognitive screening tests to evaluate for HAND. Additional studies highlighted the increasing role of neuroimaging to longitudinally assess potential changes in brain integrity in individuals on systemically suppressive therapy, and provided new CNS considerations in antiretroviral regimens.