title: Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naïve subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934.
abstract: 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).
authors: Gilead Sciences, Inc., Foster City, California 94404, USA.
authors: Nicolas A
authors: NA
authors: Margot
authors: Jeff
authors: J
authors: Enejosa
authors: Andrew K
authors: AK
authors: Cheng
authors: Michael D
authors: MD
authors: Miller
authors: Damian J
authors: DJ
authors: McColl
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000480:Alkynes; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D048588:Benzoxazines / Q000494:pharmacology / Q000627:therapeutic use; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D016679:Genome, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D020125:Mutation, Missense; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use; D000068698:Tenofovir; D017211:Treatment Failure; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D003841:Deoxycytidine; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C098320:efavirenz