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

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.