Resistance to saquinavir (Ro 31-8959), an inhibitor of human immunodeficiency virus type 1 proteinase, was studied in peripheral blood mononuclear cell-derived proviral DNA from patients undergoing prolonged treatment. A Leu90-Met exchange was the predominant resistance mutation in vivo; Gly48-Val or doubly mutant virus was rarely observed. After 8-12 months of treatment with saquinavir alone (600 mg, 3 times/day) or in combination with zidovudine (200 mg, 3 times/day), ~45% of all patients carried provirus with mutant proteinase; the incidence was lower (22%) in patients treated with a combination of saquinavir, zidovudine, and dideoxycytidine. There was a good relationship between genotypic analysis of saquinavir resistance and data from virus assays, confirming that Leu90-Met and Gly48-Val are the essential exchanges in the proteinase that determine loss of sensitivity to this inhibitor. Absence of genotypic resistance correlated with a sustained decrease in plasma viral RNA. There was a positive correlation between a Met90 mutation and some residues at natural polymorphic sites (positions 10, 36, 63, and 71).
CITATION STYLE
Jacobsen, H., Hänggi, M., Ott, M., Duncan, L. B., Owen, S., Andreoni, M., … Mous, J. (1996). In vivo resistance to a human immunodeficiency virus type 1 proteinase inhibitor: Mutations, kinetics, and frequencies. Journal of Infectious Diseases, 173(6), 1379–1387. https://doi.org/10.1093/infdis/173.6.1379
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