Comparison of genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 isolates from patients treated with stavudine and didanosine or zidovudine and lamivudine.
Sequencing of reverse-transcriptase genes and recombinant virus assays were performed on paired isolates from antiretroviral drug-naive patients randomized to stavudine and didanosine (group 1; n = 21) or zidovudine and lamivudine (group 2; n = 21) at baseline and after > or = 12 months of follow-up. The T215Y mutation emerged in 13 (61.9%) and 2 (9.5%) isolates in groups 1 and 2, respectively (P < .0001). Furthermore, in group 1, mutations associated with multidideoxynucleoside resistance were selected in 3 isolates. In group 2, all isolates carried the M184V mutation. The median fold changes in susceptibilities to zidovudine, stavudine, and lamivudine were 16.4 and 1, 2.2 and 0.6, and 4.5 and > 38 in groups 1 and 2, respectively (P < .0001, all comparisons). These results suggest that the combination of stavudine and didanosine is associated more frequently with the emergence of zidovudine resistance and a decrease in susceptibility to stavudine than the combination of zidovudine and lamivudine.
Picard
V
V
Laboratory of Virology, Hôpital Saint-Louis, Paris, France.
Angelini
E
E
Maillard
A
A
Race
E
E
Clavel
F
F
Chêne
G
G
Ferchal
F
F
Molina
J M
JM
D000328:Adult; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use*; D015224:Dideoxynucleosides / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D017354:Point Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018119:Stavudine / Q000494:pharmacology / Q000627:therapeutic use*; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*; D000099227:Abacavir
D016049:Didanosine; D015224:Dideoxynucleosides; D019259:Lamivudine; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D015215:Zidovudine; D000099227:Abacavir