Back to Search
Start Over
In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2005 Mar; Vol. 49 (3), pp. 1139-44. - Publication Year :
- 2005
-
Abstract
- Human immunodeficiency virus type 1 (HIV-1) with a lysine-to-arginine substitution at codon 65 (HIV-1(65R)) of reverse transcriptase (RT) can rapidly emerge in patients being treated with specific combinations of nucleoside analog RT inhibitors (NRTIs). A better understanding of the activity of approved and investigational NRTIs against HIV-1(65R) is needed to select optimal therapy for patients infected with this mutant and to devise strategies to prevent its emergence. Therefore, we tested a broad panel of NRTIs that differed by enantiomer, pseudosugar, and base component against HIV-1(65R) to determine how NRTI structure affects activity. Drug susceptibilities of recombinant wild-type (HIV-1(65K)) or mutant HIV-1(65R) were determined using a single-replication-cycle susceptibility assay with P4/R5 cells and/or a multiple-replication-cycle susceptibility assay with MT-2 cells. All D, L, and acyclic NRTIs were significantly less active against HIV-1(65R) than against HIV-1(65K) except for analogs containing a 3'-azido moiety. Pseudosugar structure and base component but not enantiomer influenced NRTI activity against HIV-1(65R). These findings support the inclusion of 3'-azido-3'-deoxythymidine in drug combinations to treat patients having HIV-1(65R) and to prevent its emergence.
Details
- Language :
- English
- ISSN :
- 0066-4804
- Volume :
- 49
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 15728915
- Full Text :
- https://doi.org/10.1128/AAC.49.3.1139-1144.2005