Measuring HIV-1 RNA and interferon-alpha in the cerebrospinal fluid of AIDS patients: insights into the pathogenesis of AIDS Dementia Complex

The aim of this work was to study the role of HIV replication and the role of endogenous secretion of interferon-alpha in the pathogenesis of AIDS Dem entia Complex (ADC). To accurately establish the diagnosis of ADC, 39 conse cutive HIV-positive patients who presented with immune and intellectual def iciency underwent an extensive neurological evaluation. This included magne tic resonance imaging, neuropsychological testing and a lumbar puncture. Th e levels of HIV-1 RNA were measured in the cerebrospinal fluid (CSF) and bl ood by HIV Monitor (Roche Diagnostics) and those of interferon-alpha by an in-house biological assay. The diagnosis of ADC was established in 22 cases , which included nine out of the ten patients who had a high CSF viral load (above 4 log HIV-1 RNA copy per ml). Patients receiving highly active anti retroviral therapy had low viral loads in blood and CSF. In all 22 ADC pati ents, viral load in the CSF correlated with the staging of ADC (r=0.46, P=0 .03), the CSF level of interferon-x (r=0.42, P=0.05) and with the bicaudate ratio (r=0.43, P=0.06), a measure of cerebral atrophy in the region of the caudate nucleus. Na correlation was observed between CSF and plasma HIV-1 RNA. These results show that HIV may play a role in the neurological impair ment of ADC patients possibly in part through the deleterious effect of int erferon-alpha on the central nervous system and that highly active combinat ion therapy should reduce or prevent these complications.