A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

AIDS Res Hum Retroviruses. 1998 Feb 10;14(3):255-60. Unique Identifier : AIDSLINE MED/98150880
Balzarini J; Pelemans H; Esnouf R; De Clercq E; Rega Institute for Medical Research, Katholieke Universiteit Leuven,; Belgium. Jan.Balzarini@rega.kuleuven.ac.be

Abstract: Treatment of wild-type human immunodeficiency virus [HIV-1(IIIB)]-infected cell cultures with the thiocarboxanilide UC-781 under low selective pressure (i.e., 0.01 microg/ml) resulted in the emergence of V106A RT mutant virus. On increasing drug concentrations (stepwise up to 30 microg/ml) the virus retained the V106A RT mutation but acquired the novel F227L mutation in the RT genome in addition to the L100I, K1O1I, and Y181C mutations. This multiple-mutant virus proved highly resistant to virtually all nonnucleoside RT inhibitors (NNRTIs) e.g., nevirapine, delavirdine, and loviride), but retained full sensitivity to nucleoside analogs such as AZT, ddI, (-)FTC, and 3TC. The F227 amino acid is highly conserved in HIV-1 strains and forms part of the NNRTI-binding pocket. Our model suggests a hydrophobic interaction between F227 and the chloro atom of UC-781.

Keywords: *Anilides/PHARMACOLOGY *Anti-HIV Agents/PHARMACOLOGY *Furans/PHARMACOLOGY *HIV-1/DRUG EFFECTS *HIV-1 Reverse Transcriptase/GENETICS *Mutation *Reverse Transcriptase Inhibitors/PHARMACOLOGY
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