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

Objective: The type and frequency of mutations in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase coding region observed in virus from antiretroviral therapy (ART)-experienced, zidovudine (ZDV)-naive subjects receiving stavudine (d4T)-based therapies were compared with mutations observed in virus from ART-experienced subjects with previous ZDV exposure. Methods: Plasma HIV-1 RNA was isolated from 67 ART-experienced subjects. Reverse 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_expZ_naive). Human immunodeficiency virus type 1 from 16 of 33 (48%) d_expZ_naive subjects and from 16 of 34 (47%) Z_exp subjects had thymidine analog mutations (TAMs). Multinucleoside resistance (MNR) mutations were observed in virus from 5 of 33 (15%) d_expZ_naive subjects and 3 of 34 (9%) Z_exp subjects. At least one TAM or MNR mutation was identified in 18 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 mutations can arise in subjects receiving d4T-based therapy who are naive with respect to ZDV.