PubMed · 8098408
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S Lagakos, C Pettinelli, D Stein. 1993-05-15. The Concorde trial.. https://pubmed.ncbi.nlm.nih.gov/8098408/
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Patterns of mutations associated with didanosine (ddI) resistance are still a controversial issue. The correlation between different clusters of reverse transcriptase mutations with the short-term virological activity of ddI when added to a failing regimen was examined in 40 patients. The median fall in plasma viral load at week 4 was 0.67 log10 copies/ml. There was good correlation between the median fall in plasma HIV RNA levels and the number of nucleoside-associated (P = 0.0152) or thymidine-associated (P = 0.0142) mutations. In conclusion, ddI retained substantial antiretroviral activity when the number of nucleoside-associated or thymidine-associated mutations was less than four.
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In vitro selection of HIV-1(EVK) variants resistant to highly effective nucleoside reverse transcriptase inhibitors (NNRTIs), i.e. azidothymidine (AZT) and didanosine (ddI) was performed. In case of AZT resistant mutants, subcloning by limiting dilutions was used. The isolated AZT resistant mutants and subclones had a broad spectrum of phenotypic resistance (8, 25, 53, 80, 114, 160-fold). The ddI resistant mutant possessed 10-fold resistance. The AZT resistant mutants and subclones had a high level of cross-resistance to H-phosphonate of AZT (H-phAZT) and a moderate level of cross-resistance to d4T. Still, they were effectively inhibited by a new compound, i.e. phosphonate of d4T.