Study 934 was an open-label, randomized Phase III study of emtricitabine + tenofovir DF + efavirenz (FTC + TDF + EFV) compared with lamivudine + zidovudine + efavirenz (3TC + ZDV + EFV) in antiretroviral therapy-naïve HIV-1 infected subjects. Baseline genotyping revealed the presence of primary nonnucleoside reverse transcriptase inhibitor resistance (NNRTI-R) in 22 of 509 enrolled patients (4.3%, 11 subjects in each group). The 487 subjects without baseline NNRTI-R formed the primary efficacy population (modified intent-to-treat population). Through 144 weeks, 50 of 487 modified intent-to-treat subjects (FTC + TDF + EFV, n = 19; 3TC + ZDV + EFV, n = 31) were analyzed for resistance development after virologic failure. NNRTI-R, primarily the K103N mutation, was the most common form of resistance that developed in both groups. No subject on FTC + TDF + EFV developed the K65R mutation. Significantly fewer subjects on FTC + TDF + EFV compared with 3TC + ZDV + EFV developed the M184V/I mutation (two versus 10, respectively, P = 0.021). Thymidine analog mutations developed in two subjects on 3TC + ZDV + EFV. Subjects with baseline NRTI genotypic resistance (TAMs, n = 13) or non-B HIV-1 subtypes (n = 28) showed no evidence of reduced treatment responses in either group. Nine of 22 patients with baseline NNRTI-R experienced virologic failure (FTC + TDF + EFV, n = 4; 3TC + ZDV + EFV, n = 5); seven of nine developed M184V/I and/or additional NNRTI-R, but none developed K65R. Baseline NNRTI-R was significantly associated with virologic failure in both groups (P < 0.001).
From Gilead Sciences, Inc., Foster City, California.
Received for publication November 13, 2008; accepted May 11, 2009.
This study was supported entirely by Gilead Sciences, Inc.
Presented in part at the 11th European AIDS Conference, October 24-27, 2007, Madrid, Spain (Poster P3.1/08).
Correspondence to: Damian J. McColl, PhD, Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404 (e-mail: Damian.McColl@gilead.com).