Resistance profiles of emtricitabine and lamivudine in tenofovir-containing regimens.

A G Marcelin, C Charpentier, M Wirden, R Landman, M A Valantin, A Simon, C Katlama, P Yeni, D Descamps, C Aubron-Olivier, V Calvez

Université Pierre et Marie Curie-Paris 6, UMR S-943, Paris F-75013, France. anne-genevieve.marcelin@psl.aphp.fr

The Journal of antimicrobial chemotherapy 2012 Jun

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To compare the frequency of the selection of the M184V/I resistance mutation in HIV-infected patients who experienced virological failure while receiving emtricitabine (FTC) or lamivudine (3TC), administered with tenofovir disoproxil fumarate (TDF) and either efavirenz (EFV) or a ritonavir-boosted protease inhibitor (PI; lopinavir or atazanavir). Patient data held at two clinical centres in France were analysed retrospectively. Eligible patients had experienced virological suppression (plasma HIV RNA <200 copies/mL) for ≥ 6 months before experiencing their first virological failure (at least two measurements of plasma HIV RNA ≥ 200 copies/mL). Of the 880 patients eligible for the study, 278 patients had experienced virological failure while receiving FTC + TDF + ritonavir-boosted PI, 257 while receiving FTC + TDF + EFV, 178 while receiving 3TC + TDF + EFV and 167 while receiving 3TC + TDF + ritonavir-boosted PI. Proportions of patients harbouring the M184V/I mutation were 24% (n = 62) for those who received FTC + TDF + EFV versus 51% (n = 91) for 3TC + TDF + EFV (P < 0.0001; Fisher's exact test); proportions were 11% (n = 30) for FTC + TDF + ritonavir-boosted PI versus 22% (n = 37) for 3TC + TDF + ritonavir-boosted PI (P = 0.002; Fisher's exact test). The use of lamivudine versus emtricitabine (P = 0.001), non-nucleoside reverse transcriptase inhibitors versus ritonavir-boosted PIs (P = 0.01) and the level of viral load at the time of virological failure (P = 0.01) were associated with selection of the M184V/I mutation (logistic regression analysis). Emtricitabine and lamivudine showed differing resistance profiles when administered in combination with tenofovir disproxil fumarate and either efavirenz or a ritonavir-boosted PI. The prevalence of the M184V/I resistance mutation was significantly lower in patients who received emtricitabine and tenofovir disoproxil fumarate than in those who received lamivudine and tenofovir disoproxil fumarate.

Citation

A G Marcelin, C Charpentier, M Wirden, R Landman, M A Valantin, A Simon, C Katlama, P Yeni, D Descamps, C Aubron-Olivier, V Calvez. Resistance profiles of emtricitabine and lamivudine in tenofovir-containing regimens. The Journal of antimicrobial chemotherapy. 2012 Jun;67(6):1475-8