Independent HIV replication in paired CSF and blood viral isolates during antiretroviral therapy

Background: The goal of highly active antiretroviral therapy in HIV-infected patients is to reduce plasma viral load (VL) below quantifiable levels. Mutations associated with drug resistance within the HIV-1 genome can limit therapeutic success. Low VL implicates a low risk of emergence of resistant mutants. Whether there is divergent development of HIV strains in different biologic compartments is not understood. Methods: The authors studied VL and the occurrence of mutations conferring resistance in viral genomes isolated from blood and CSF samples of 23 HIV-infected patients. They determined sequences of HIV-1 RNA by reverse transcriptase PCR amplification and direct sequencing. They measured resistance to antiretroviral drugs genotypically by detection of drug-related point mutations and VL by a branched-DNA assay. Results: Amplification of HIV was successful even in patients with plasma or CSF VL below detection limit. VL was considerably lower in CSF as compared with blood (p < 0.0001). There was no correlation between CSF and plasma VL. The mutational pattern in viral copies derived from blood and CSF was not identical. Ten (9%) of the total number of 118 mutations associated with drug resistance occurred in blood isolates only; 14 (11%) were detected exclusively in CSF strains. Conclusion: There is evidence for viral replication at HIV RNA levels less than 50/mL. The results suggest divergent evolution of HIV-1 in different biologic compartments. The presence of resistant mutants in the CSF may escape regular diagnostic in blood. Therapeutic success may fail after adapting therapy to genotypic resistance patterns detected in one compartment only.