Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus lamivudine combination therapy.
OBJECTIVE
Mutations usually associated with zidovudine exposure have been observed in zidovudine-naive patients treated by stavudine in combination. These mutations were named thymidine analogue mutations (TAMs). This fact, combined with phenotypical and biochemical findings provided additional evidence for cross-resistance between zidovudine and stavudine. A recent genotypic study in naive patients receiving stavudine/didanosine combination showed emergence of TAMs and a multidrug-resistance mutation (MDR), Q151M, in 36 and 10% of cases, respectively. Stavudine plus lamivudine is one of the most used binucleoside associations in the antiretroviral combinations. The objective of this study was to assess the genotypic changes in the HIV-1 reverse transcriptase (RT) gene in antiretroviral-naive patients treated by stavudine plus lamivudine.


METHODS
We analysed the RT gene of 44 HIV-1 patients, naive of antiretroviral therapy, who were treated for 24 or 48 weeks with stavudine/lamivudine.


RESULTS
At the end of the follow-up, all patients acquired the lamivudine-associated mutation M184V. Only two subjects (4.5%) developed a TAM (T215Y; M41L), one subject developed a V75T/A mutation and one subject developed the particular MDR pattern F116Y, Q151M.


CONCLUSIONS
Our study clearly demonstrated that naive subjects treated with stavudine/lamivudine for 24-48 weeks selected a low rate of TAMs and MDR Q151M. One hypothesis explaining these results could be the development of the M184V mutation.
Mouroux
M
M
Department of Virology, Pitié-Salpêtrière Hospital, Paris, France.
Descamps
D
D
Izopet
J
J
Yvon
A
A
Delaugerre
C
C
Matheron
S
S
Coutellier
A
A
Valantin
M A
MA
Bonmarchand
M
M
Agut
H
H
Massip
P
P
Costagliola
D
D
Katlama
C
C
Brun-Vezinet
F
F
Calvez
V
V
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005838:Genotype; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D009154:Mutation; D018119:Stavudine / Q000008:administration & dosage*; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine; D054303:HIV Reverse Transcriptase