Long-term virological effect of highly active antiretroviral therapy on cerebrospinal fluid and relationship with genotypic resistance

Abstract

The objective of this study was to assess the long-term virological response in cerebrospinal fluid (CSF) in patients treated with highly active antiretroviral therapy (HAART) and to compare this response to CSF and plasma human immunodeficiency virus (HIV) drug resistance profiles. Paired CSF and plasma specimens were drawn from 18 patients receiving HAART at baseline and after 9 to 70 months of therapy. At baseline, median HIV-1 RNA concentrations were 4.13 log10 copies/ml in CSF and 5.31 log10 copies/ml in plasma. At the time of on-therapy CSF sampling, HIV-1 RNA was undetectable in CSF from 13/18 patients (72%), and in plasma from 9/18 patients (50%). The genotypic analysis at baseline revealed reverse transcriptase (RT) resistance mutations in 7 of 11 (64%) CSF samples and in 8 of 11 (73%) plasma samples. No patient had protease resistance mutations, except for secondary mutations. At the time of virological failure in CSF, new RT and protease resistance mutations were found in both CSF and plasma of the two patients with both baseline and on-treatment paired evaluations. At long-term follow-up, the proportion of patients failing to respond virologically was lower in CSF than in plasma. Virological failure in CSF was associated with failure to respond in plasma and onset of new drug resistance mutations in both compartments.