Reduced concentrations of HIV-RNA and TNF-alpha coexist in CSF of AIDS patients with progressive multifocal leukoencephalopathy

Abstract

OBJECTIVES To confirm reduced human immunodeficiency virus type-1 (HIV-1) burden in the CSF of patients with progressive multifocal leukoencephalopathy (PML) and to verify whether this viral load coincides with the absence of inflammatory changes in the CSF. METHODS Paired CSF and plasma samples from 17 patients with PML, 26 with non-PML cerebral opportunistic infections, nine with HIV-1 leukoencephalopathy (HIVE), and 12 neurologically asymptomatic AIDS patients were subjected to HIV-RNA titration. Tumour necrosis factor (TNF)-α was also measured and the CSF albumin: serum albumin ratio (QAlb) was calculated. RESULTS The CSF HIV-1 burden of patients with PML did not differ from that of neurologically asymptomatic patients (p=0.21), but was significantly lower than CSF burden of the remaining patients (non-PML opportunistic infections, p<0.001; HIVE, p<0.001). QAlb was normal for all neurologically asymptomatic patients, for 86.6% patients with PML, and 62.5% patients with HIVE (p=0.09). QAlb was altered in 91.6% patients with non-PML opportunistic infections. TNF-α in CSF was higher in patients with non-PML opportunistic infections (p<0.001) and those with HIVE (p<0.001) than in patients with PML who consistently had TNF-α concentrations<10 pg/ml. CONCLUSIONS These results, while indicating a reduced HIV replication in CSF of patients with PML which might serve as a disease marker, emphasise the increased CSF HIV-RNA concentration in patients with HIVE and patients with non-PML opportunistic infections. Low concentrations of HIV-RNA in CSF coincide with reduced TNF-α concentrations, possibly due to particular features of PML compared with other opportunistic infections as it develops without detectable inflammatory changes in the CSF.