Antiretroviral resistance mutations in human immunodeficiency virus type 1reverse transcriptase and protease from paired cerebrospinal fluid and plasma samples

Twenty-four adults infected with human immunodeficiency virus type 1 (HIV-1 ) with central nervous system symptoms were studied for antiretroviral resi stance mutations in HIV-1 RNA obtained from paired cerebrospinal fluid (CSF ) and plasma samples. Paired sequences were obtained from 21 and 13 patient s for reverse transcriptase (RT) and for protease, respectively. Mutations conferring resistance to the RT inhibitors zidovudine, lamivudine, or nevir apine were detected in 14 patients, including 11 pretreated and 3 drug-naiv e subjects. The mutation patterns in the 2 compartments were different in m ost patients, Genotypic resistance to protease inhibitors was detected in b oth plasma and CSF from 1 patient treated with multiple protease inhibitors . However, accessory protease inhibitor resistance mutations at polymorphic sites were different in plasma and CSF in several patients. Partially inde pendent evolution of viral quasispecies occurs in plasma and CSF, raising t he possibility that compartmentalization of drug resistance may affect resp onse to antiretroviral treatment.