Thymidine-analog and multi-nucleoside resistance mutations are observed inboth zidovudine-naive and zidovudine-experienced subjects with viremia after treatment with stavudine-containing regimens

Objective: The type and frequency of mutations in the human immunodeficienc y virus type 1 (HIV-1) reverse transcriptase coding region observed in viru s from antiretroviral therapy (ART)-experienced, zidovudine (ZDV)-naive sub jects receiving stavudine (d4T)-based therapies were compared with mutation s observed in virus from ART-experienced subjects with previous ZDV exposur e. Methods: Plasma HIV-1 RNA was isolated from 67 ART-experienced subjects. Re verse transcriptase mutations were assessed by sequencing polymerase chain reaction products. Results: Thirty-four subjects (51%.) were ZDV-experienced (Z(exp)) and 33 ( 49%) were ZDV-naive and d4T-experienced (d(exp)Z(naive)). Human immunodefic iency virus type 1 from 16 of 33 (48%) d(exp)Z(naive) subjects and from 16 of 34 (47%) Z(exp) subjects had thymidine analog mutations (TAMs). Multinuc leoside resistance (MNR) mutations were observed in virus from 5 of 33 (15% ) d(exp)Z(naive) subjects and 3 of 34 (9%) Z(exp) subjects. At least one TA M or MNR mutation was identified in IS of 33 (55%) of the former and in 19 of 34 (56%) of the latter group. Conclusions: These results confirm recent reports that TAMs and MNR mutatio ns can arise in subjects receiving d4T-based therapy who are naive with res pect to ZDV.