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3rd International Workshop on HIV Drug Resistance2-5 August 1994, Kauai, Hawaii, USA |
NATURAL OCCURRENCE OF RESISTANCE MUTATIONS IN THE pol GENE OF HIV-1 ISOLATES
Int Wkshop HIV Drug Res 1994 Aug 2-5;3:21 (abstract no. 20)
I. Najera1*, D.D Richman2, I. Olivares1, J.M. Rojas1, R Najera1 and C. Lopez-Galindez1
1Instituto de Salud Carlos III, Majadahonda, Spain;
2University of California San Diego, Departments of Pathology and Medicine, San Diego, USA;
*Present address: Wellcome Research Laboratories, UK
We report the detection of mutations in the reverse transcriptase (RT) of two samples from AZT-treated patients previously related to nevirapine ( Richman et al., 1991), ddC - (Fitzgibbon et al., 1992) and D4T - (Lacey and Larder, 1994) resistance.
Sample 302 acquired a mutation in codon 181 (TAT→TGT) leading to the amino acid substitution Y→C. Sample 304 showed several mutations at codons related to drug-resistance, 69 (ACT→GAT, leading to amino acid substitution T→D) and 75 (GTA→ATG, leading to amino acid residue change V→M).
The appearance of these mutations occurred in the absence of drug-selective pressure, thus pointing out the contribution that the extensive genetic variability plays in the frequent emergence of HIV-1 RT inhibitors-resistance.
Richman DD, Shih C, Lowry I, et al. “Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture” Proc. Natl Acad Sci USA 1991; 88: 11241-11245.
Fitzgibbon JE, Howell RM, Haberzettl CA, et al. “Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2´,3´-dideoxycytidine” Antimicrob Agents Chemother. 1992 Jan;36(1):153-7.
Lacey SF and Larder BA “Novel mutation (V75T) in human immunodeficiency virus type 1 reverse transcriptase confers resistance to 2´,3´-didehydro-2´,3´-dideoxythymidine in cell culture” Antimicrob Agents Chemother. 1994 Jun;38(6):1428-32.
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1994-08-02
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