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

Background: The goal of highly active antiretroviral therapy in HIV-infecte d patients is to reduce plasma viral load (VL) below quantifiable levels. M utations 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 differen t biologic compartments is not understood. Methods: The authors studied VL and the occurrence of mutations conferring resistance in viral genomes isol ated from blood and CSF samples of 23 HIV-infected patients. They determine d sequences of HIV-1 RNA by reverse transcriptase PCR amplification and dir ect sequencing. They measured resistance to antiretroviral drugs genotypica lly by detection of drug-related point mutations and VL by a branched-DNA a ssay. Results: Amplification of HIV was successful even in patients with pl asma or CSF VL below detection limit. VL was considerably lower in CSF as c ompared with blood (p < 0.0001). There was no correlation between CSF and p lasma VL. The mutational pattern in viral copies derived from blood and CSF was not identical. Ten (9%) of the total number of 118 mutations associate d with drug resistance occurred in blood isolates only; 14 (11%) were detec ted exclusively in CSF strains. Conclusion: There is evidence for viral rep lication at HIV RNA levels less than 50/mL. The results suggest divergent e volution of HIV-1 in different biologic compartments. The presence of resis tant mutants in the CSF may escape regular diagnostic in blood. Therapeutic success may fail after adapting therapy to genotypic resistance patterns d etected in one compartment only.