Pastore G

Neurological disorders during HIV-1 infection correlate with viral load in cerebrospinal fluid but not with virus phenotype

Objectives:To verify the compartmentalization of HIV-1 within the central nervous system (CNS) and to define whether viral phenotype of HIV-1 isolates from cerebrospinal fluid (CSF) samples and CSF viral load correlate with the presence and type of neurological disorders. Methods:A total of 33 HIV-1-infected patients with and without neurological disorders were included in the study. HIV-1 isolation from paired CSF and peripheral blood mononuclear cell (PBMC) samples was attempted by a standard cocultivation technique; the biological phenotype of HIV-1 isolates was assessed by the MT-2 cell assay. CSF and plasma HIV-RNA levels were measured by a quantitative reverse transcripase–polymerase chain reaction. Results:The rate of HIV-1 isolation from CSF and PBMC was 66% (22 isolates) and 85% (28 isolates), respectively. Seventeen out of 22 (77%) CSF HIV-1 isolates were characterized as non-syncytium-inducing, and 15 out of 28 (68%) isolates from PBMC were typed as syncytium-inducing (SI). The presence of SI isolates in CSF was limited to patients with HIV-1-, cytomegalovirus- or JC virus-related disorders and was often associated with high levels of HIV-1 RNA in the CSF. Discussion:Our results demonstrate a correlation between high levels of HIV RNA in CSF and the presence of neurological disorders thus indicating a possible role for HIV-1 RNA in the CSF as a biological marker of neurological disease. The finding of viruses with a different phenotype in paired CSF and PBMC indicates that HIV-1 may evolve differently in the brain and in the blood. This suggests compartmentalization of HIV-1 within the CNS.