REVERSE-TRANSCRIPTASE SEQUENCE OF PAIRED ISOLATES OF CEREBROSPINAL-FLUID AND BLOOD FROM PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUSTYPE-1 DURING ZIDOVUDINE TREATMENT

Human immunodeficiency virus type 1 (HIV-1) isolates obtained from the blood of patients undergoing treatment with 3'-azido-3'-deoxythymidin e (zidovudine [AZT]) show a decreased sensitivity to the drug in vitro . The aim of the present study was to determine if HIV-1 variants resi stant to AZT are present also in the brain compartment. We selected se quential HIV-1 isolates from the blood and the cerebrospinal fluid (CS F) of six patients with HIV-1 infection undergoing AZT therapy for a t ime varying between 1 and 3 years. The isolates were used to infect pe ripheral blood mononuclear cell cultures which were used to prepare vi ral DNA. The viral DNA was amplified by PCR and then directly sequence d. Analysis of the reverse transcriptase (RT) sequence of the isolates from the CSF during therapy demonstrated that CSF-resistant isolates are characterized by the same mutations documented in resistant isolat es from the blood compartment. Isolates obtained from one patient (pat ient 3) showed the same two mutations (codons 70 and 215) in blood and CSF, whereas isolates obtained from an additional four patients prese nted a different pattern of mutations in the two compartments. We also analyzed the degree of amino acid homology between RT sequences from blood and CSF isolates in patients before and during AZT treatment. Th e percentages of amino acid variations were approximately equal when i solates from the same or different compartments were considered. Exclu ding the codons involved in AZT resistance, the time point of sampling did not affect RT variations during therapy significantly. In conclus ion, our studies show that AZT-resistant HIV-1 can be found in the CSF of patients undergoing treatment The mutations linked to AZT resistan ce in the CSF isolates are the same as those identified in AZT-resista nt isolates from blood.