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(exp)Z(naive)). Human immunodeficiency 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). Multi-nucleoside 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 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.
Ross
L
L
Department of Clinical Virology, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA. llr8156@gsk.com
Henry
K
K
Paar
D
D
Salvato
P
P
Shaefer
M
M
Fisher
R
R
Liao
Q
Q
St  Clair
M
M
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018119:Stavudine / Q000494:pharmacology* / Q000627:therapeutic use; D013936:Thymidine / Q000031:analogs & derivatives / Q000235:genetics; D014766:Viremia / Q000188:drug therapy; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D018119:Stavudine; D054303:HIV Reverse Transcriptase; D013936:Thymidine