Evaluation of mixtures of wild-type HlV-1 and HIV-1 with resistance point mutations against reverse transcriptase inhibitors

The presence of resistance-related mutations in 185 serial proviral DNA sam ples from 108 HIV-infected patients was monitored using the line probe assa y (LiPA). The proportions of wild-type and mutant Virus in each sample were determined. Subsequent samples from the same patient were analysed. Resistance mutations were detected in 58 of 108 patients studied (53.7%), 5 3 of 73 (72.6%) treated with antivirals and 5 of 35 (14.2%) untreated. The mutations were against zidovudine (51), lamivudine (1), zidovudine and lami vudine (4), zidovudine and zalcitabine (1) and zidovudine and didanosine (1 ). Among the 58 patients with resistant virus, 168 related mutations were o bserved: 161 to zidovudine (90 in codon 70, 25 in codon 41 and 46 in codon 215), 5 to lamivudine (codon 184), 1 to zalcitabine (codon 69) and 1 to did anosine (codon 74). Mixtures of wild-type and resistant mutants were detect ed in 76 of 90 (84.4%) mutated at codon 70, 28 of 46 (60.80%) mutated at co don 215 and in 21 of 25 (84%) mutated at codon 41. The mutations at codon 1 84 were mixtures of wild-type and resistant in 4 of 5 samples. The agreement between LiPA and sequencing was 96.5%. LiPA was more sensitiv e for the detection of mutants that were present at law frequency. The anal ysis of sequential samples from the same patient allowed evaluation of the dynamics of appearance of the resistant mutants.