High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients

Abstract

In ARV-naive HIV-1-infected patients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear.

Treatment Outcomes of Recommended First-Line Antiretroviral Regimens in Resource-Limited Clinics

“…[5][6][7][8][9][10][11][12][13][14][15][16] Yet 2 small studies comprising less than 42 patients did suggest that the combination of TDF + NVP and emtricitabine or lamivudine (XTC) has higher virologic failure rates than anticipated. [17][18][19] Despite the lack of difference in the primary endpoints between the NVP/TDF/emtricitabine (FTC) and the atazanavir/r + TDF + FTC arms in the ARTEN trial, there were more participants in the NVP arms than the atazanavir/ritonavir arm who discontinued study drugs because of adverse events (13.6% vs. 2.6%) or lack of efficacy (8.4% vs. 1.6%). 11 The 2011 US DHHS guidelines list NVP as an acceptable but not a preferred or an alternative first-line drug and continue to place a warning on combination of NVP and TDF.…”

Perfil de resistencia del VIH-1 a anti-retrovirales en pacientes con fallo virològico: Hospital Roosevelt-Guatemala 2008-2012

“…Tal hecho fue reportado por Gallant y cols., quienes detectaron 21% de K65R en la combinación de TDF + 3TC que no permitió obtener una adecuada supresión viral 26 . Aunado a esto, se ha evidenciado una fuerte asociación para la selección de K65R con el uso de NVP y sus mutaciones de resistencia Y181C/G y G190A/S [27][28][29][30] . Interesantemente, en el caso de Guatemala, todos los pacientes con K65R tenían antecedente de uso, además de TDF, al menos uno de los siguientes: NVP, d4T, AZT o ddI; sumado a esto, más de dos tercios tenían al menos una de estas mutaciones Y181C/G o G190A/S.…”

Point Mutations Associated with HIV-1 Drug Resistance, Evasion of the Immune Response and AIDS Pathogenesis

“…Thus, the K65R point mutation commonly causes intermediate resistance to tenofovir (TDF), ABC, ddI, 3TC and FTC (Table 2), low level resistance to d4T, and increased susceptibility to AZT (Antinori et al, 2007;Lanier et al, 2004b). There is a body of evidence suggesting that K65R mutation occurs more commonly in low-income countries when patients with nonsubtype B HIV-1 strains are treated with d4T/ddI and d4T/3TC Hawkins et al, 2009) or TDF/3TC (Rey et al, 2009). In comparison to K65R, L74V point mutation causes intermediate resistance to ddI and ABC, and a slight increase in susceptibility to AZT and TDF (Rhee et al, 2006b).…”