Abstract

Fixed-dose combination antiretroviral therapy administered as a single-tablet regimen (STR) may improve virologic suppression rates. The effect of STRs on development of resistance when virologic failure occurs on STRs is not known.To compare the rate of emergent drug resistance mutations (DRMs) on first-line therapy with coformulated tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/efavirenz (EFV) as an STR versus TDF, lamivudine (3TC) or FTC, and EFV given as non-STR.Patients from eight cohorts and four randomized clinical trials who received first-line antiretroviral therapy with Atripla (STR group) or with TDF + FTC/3TC + EFV (non-STR group) were eligible if a genotypic resistance test was available immediately after the first episode of viral failure. The DRM list from the 2013 version of IAS-USA was used.One hundred and eighty-six patients were included in the final analysis, 122 (65.6%) from eight cohorts and 64 (34.1%) from four randomized clinical trials. The overall proportion of patients with at least one DRM at viral failure was 67.7%, including 53.4% (31 of 58) in the STR group vs. 74.2% (95 of 128) in the non-STR group (P?=?0.005). Among patients exclusively from cohorts, at least one DRM was detected in 53.4% (31 of 58) in the STR group vs. 78.1% (50 of 64) in the non-STR group (P?=?0.004). DRMs for individual drugs were: TDF, 15.5 vs. 16.4% (P?=?0.87); 3TC/FTC, 31 vs. 35.2% (P?=?0.58); and NNRTI, 51.7 vs. 65.6% (P?=?0.07). The proportion of patients with an M184V/I among the 128 patients who received FTC was 32.8 vs. 36.2% among the 58 treated with 3TC (P?=?0.65).Compared to patients receiving the STR-Atripla, those receiving the same components individually in a non-STR regimen have a statistically significantly increased risk of selecting for DRMs associated with their drugs on failure.

View details for DOI 10.1097/QAD.0000000000000424

View details for PubMedID 25574957