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Journal of Clinical Microbiology, 02 1995, 352-355, Vol 33, No. 2
Copyright © 1995 by the American Society for Microbiology. All rights reserved.

Reverse transcriptase sequence of paired isolates of cerebrospinal fluid and blood from patients infected with human immunodeficiency virus type 1 during zidovudine treatment

M Di Stefano, F Sabri, T Leitner, B Svennerholm, L Hagberg, G Norkrans and F Chiodi
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.

Human immunodeficiency virus type 1 (HIV-1) isolates obtained from the blood of patients undergoing treatment with 3'-azido-3'-deoxythymidine (zidovudine [AZT]) show a decreased sensitivity to the drug in vitro. The aim of the present study was to determine if HIV-1 variants resistant to AZT are present also in the brain compartment. We selected sequential HIV-1 isolates from the blood and the cerebrospinal fluid (CSF) of six patients with HIV-1 infection undergoing AZT therapy for a time varying between 1 and 3 years. The isolates were used to infect peripheral blood mononuclear cell cultures which were used to prepare viral DNA. The viral DNA was amplified by PCR and then directly sequenced. 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 isolates from the blood compartment. Isolates obtained from one patient (patient 3) showed the same two mutations (codons 70 and 215) in blood and CSF, whereas isolates obtained from an additional four patients presented 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. The percentages of amino acid variations were approximately equal when isolates from the same or different compartments were considered. Excluding the codons involved in AZT resistance, the time point of sampling did not affect RT variations during therapy significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

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