Background:  To address the issue of independent HIV-1 evolution within the central nervous system (CNS) and study the origin of HIV-RNA extracted from the cerebrospinal fluid (CSF).

Methods:</.b>  Longitudinally derived paired blood and CSF samples and autopsy samples from ventricular CSF, frontal cortex, parietal sub-cortex and spleen were collected from 3 HIV-1-infected patients receiving antiretroviral treatment and presenting with neurological symptoms before death. The samples were gathered over a period of 8 months in patient 1, 1.5 months in patient 2, and 63 months in patient 3. HIV-RNA from patient isolates was amplified using an in-house RT-PCR assay and regions for reverse transcriptase (RT), protease and V3 were sequenced and phylogenetically compared by distance matrix method. The presence of drug-resistance mutations was studied.

Results:  Patient 1:  protease sequences of isolates from CSF and brain tissue contained a secondary drug mutation, L63P, and clustered separately from blood and spleen isolates, which contained secondary mutations V77I and A71V. However, the RT and V3 sequences of the last CSF sample grouped with samples from blood and spleen and contained a primary NNRTI resistance mutation, K103N, together with its paired blood sample. Patient 2:  CSF isolates were closer linked to the blood sample than to the isolates from brain tissue, although the blood sample contained a primary RT-related mutation, T215Y, and two secondary mutations K70R and K219Q. Patient 3:  except for the V3 sequence from the last blood sample, there was not much sequence diversity of isolates.

Conclusions:  A different pattern of drug resistance mutations could be found in the CNS as compared with the peripheral circulation and brain tissue samples clustered, with the exception of patient I, separately from blood samples. The main source of HIV-RNA in CSF seems to differ in different patients and may shift during different stages of infection.

Keywords: HIV-1 isolates; CNS compartment; Evolution