Mutations conferring resistance to zidovudine diminish the antiviral effect of stavudine plus didanosine.

摘要: This study evaluated the influence of zidovudine (ZDV) resistance mutations on antiviral effect combination stavudine (D4T) plus didanosine (ddI) in patients treated previously with ZDV zalcitabine (ddC). Twenty who had been ddC for a median duration 11 months (range, 7-42 months) were switched to D4T (40 mg twice day [BID]) + ddI (200 BID) an open pilot lasting 6 months. The CDC classes A (n = 10) and B 10). baseline CD4 count was 285/mm(3) plasma virus RNA (Amplicor HIV Monitor RT-PCR assay) 4.6 log copies/ml. Population-based sequence analysis detected associated reverse transcriptase (RT) inhibitors RT domain from samples 13/20 (65%) patients. Twelve (3 T215Y - M41L L210W; 3 M41L; 2 T215Y; 1 K70R) patient multi-dideoxynucleoside mutation (QI5IM). Patients significantly lower suppression after (median reduction -0.5 -0.1 log) than remaining (-1.6 -2 log). Fifty percent wild-type viruses undetectable 24 weeks therapy, whereas all those mutated concentration > copies/ml at week (P <.05). Our finding may have implications when deciding second line therapy three or four drugs that includes two new nucleoside analogues. Cross-resistance between analogues deserves maximal attention ensure optimal antiretroviral design algorithms management based genotypic testing.