Early HIV-1 infection of the central nervous system

Abstract

There is a consensus of opinion that central nervous system (CNS) involvement takes place in a large proportion of patients with the acquired immune deficiency syndrome (AIDS). However, uncertainty still remains about how often and how early the CNS is infected during the early asymptomatic stage as some researchers still believe that low copy of human immunodeficiency virus type 1 (HIV-1) identified in the brains using polymerase chain reaction (PCR) represents HIV harboured in the infected cells trapped in cerebral blood vessels. In this review, the neurological abnormalities in HIV-1 positive pre-AIDS individuals are discussed from three points of view: neuropsychiatric and neurophysiological, involvement of cerebrospinal fluid (CSF) and brain pathology. In particular, our investigations of the brains of asymptomatic individuals have demonstrated that HIV-1 DNA was present in about half (17/36) of brains studied (copy numbers of HIV-1 DNA were detected and the possibility of contamination from the blood was calculated and excluded). Astro- (34/36) and micro- (31/36) gliosis and meningitis (11/36) were found. Immune activation, revealed by elevated expression of major histocompatibility complex (MHC) class II antigens, was previously demonstrated in the brains of patients with AIDS and was also present before the development of AIDS. Furthermore, demonstration of highly expressed cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, 4, 6) possibly explains the neuropathological changes and neuronal damage (confirmed by the demonstration of apoptotic neurons by in situ end labelling) seen in these brains. We conclude that HIV-1 is present in the brains of HIV-1 infected individuals at early stages of the infection and that HIV-1 induces brain damage in a direct as well as indirect way. This is a worrying conclusion which makes it mandatory to reconsider the time at which treatment must be applied in HIV-1 infection.