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  • Title: 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.
    Author: Mouroux M, Descamps D, Izopet J, Yvon A, Delaugerre C, Matheron S, Coutellier A, Valantin MA, Bonmarchand M, Agut H, Massip P, Costagliola D, Katlama C, Brun-Vezinet F, Calvez V.
    Journal: Antivir Ther; 2001 Sep; 6(3):179-83. PubMed ID: 11808752.
    Abstract:
    OBJECTIVES: 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.
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