Predictive factors and selection of thymidine analogue mutations by nucleoside reverse transcriptase inhibitors according to initial regimen received.
Thymidine analogue mutations were determined and compared in patients who received zidovudine monotherapy and added didanosine or zalcitabine, and in patients who started with one of these dual nucleoside combinations. Although patients who started in the era of zidovudine monotherapy had a longer duration of therapy compared with the other group, there was no statistical difference in the number of mutations between the two groups. However, thymidine analogue mutations were more frequent in patients who added didanosine to zidovudine monotherapy compared with those who added zalcitabine. Patients who started with a dual nucleoside combination developed 215Y/F first, followed by 215Y/F+41L, then 215Y/F+41L+210W, then 215Y/F+67N+70R+41L or 219Q/E, and then 215Y/F+41L+67N+70R+219Q/E. Patients who started with zidovudine monotherapy had a different pathway with the mutation at codon 70 appearing first, followed by 215Y/F+70R or 210W, then 215Y/F+41L+210W, then 215Y/F+67N+70R+219Q/E, and then 215Y/F+41L+67N+70R+210W. Medication adherence was associated with the number of mutations in both groups of patients. Two distinct mutational patterns were noted. The first pattern involved mutations at codons 41, 210 and 215, while the second involved mutations at codons 67, 70 and 219.
Flandre
Philippe
P
INSERM SC10, Villejuif, France. flandre@vjf.inserm.fr
Descamps
Diane
D
Joly
Veronique
V
Meiffrédy
Vincent
V
Tamalet
Catherine
C
Izopet
Jacques
J
Aboulker
Jean-Pierre
JP
Brun-Vézinet
Françoise
F
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009154:Mutation; D011237:Predictive Value of Tests; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012641:Selection, Genetic; D013936:Thymidine / Q000031:analogs & derivatives*; D016047:Zalcitabine / Q000494:pharmacology / Q000627:therapeutic use; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D016047:Zalcitabine; D054303:HIV Reverse Transcriptase; D016049:Didanosine; D013936:Thymidine