The multifactorial pathways towards resistance to the cytosine analogues emtricitabine and lamivudine: evidences from literature.

Letter e The article by Bulteel et al., published in the September issue of the journal, has investigated the rate of M184V emergence in patients receiving HAART combinations containing efavirenz (EFV), tenofovir (TDF) and lamivudine (3 TC) or emtricitabine (FTC) within the UK Collaborative HIV Cohort. By analyzing 304 genotypic resistance tests, the authors asserted that, although patients receiving 3 TC-based regimens were more likely to develop M184V than those receiving FTC-based regimens (event rate: 0.55 [95%CI: 0.28e0.96] for 3 TC versus 0.34 [95%CI: 0.21e0.46] for FTC), this association was not statistically significant in both univariable and multivariable models. These results are different from those reported in previous studies from our and other groups showing a significant decrease in M184V emergence in patients failing FTC þ TDF-based compared to 3 TC þ TDF-based HAART (Table 1). The lower prevalence of M184V in FTCcontaining regimen was also supported by a recently published letter showing a strong trend (P Z 0.051) towards higher rates of resistance to the 3 TC containing regimen 5.5 (1.8e12.8) per 1000 patient years when compared with the FTC containing regimens 1.7 (0.8e3.2) per 1000 patient years. Such discrepancy in M184V prevalence can be explained by the profound differences in the dataset of patients analyzed. The most striking difference is represented by the fact that the studies by our and other groups have analyzed viremic patients at the time of starting a FTC þ TDFor 3 TC þ TDF-containing HAART. Conversely, Bulteel et al. have analyzed a quite heterogeneous population composed for around 50% by patients starting FTC þ TDFor 3 TC þ TDF-containing regimen during virological suppression (Table 1). In Bulteel’s study, 49.9% of 3 TC-treated patients and 46.1% of FTC-treated patients had a plasma HIV-1 RNA <50 copies/ml at the time of starting 3 TC/FTC-containing therapy. The negative correlation between baseline viremia and drug resistance emergence is well known, and it is supported also by Bulteel’s study showing that a viremia >50 copies/ml at the time of starting 3 TC/FTC containing therapy correlates with an