title: Baseline genotype as a predictor of virological failure to emtricitabine or stavudine in combination with didanosine and efavirenz.
abstract: The presence of drug-associated mutations among ART-naive, HIV-1(+) patients may compromise the response to antiviral therapy. We evaluated the effect of preexisting drug-associated resistance mutations to the response in treatment-naive patients to therapy with emtricitabine (FTC) or stavudine (d4T) in combination with didanosine (ddI) and efavirenz (EFV). Study FTC-301A compared emtricitabine once daily (QD) with stavudine twice daily in combination with didanosine and efavirenz in ART-naive patients. Genotypic analysis was performed on baseline plasma HIV-1 RNA for all available samples and at time of virologic failure (VF). Drug resistance mutations present at baseline were evaluated as predictors of VF using logistic regression. VF rates were compared between subgroups using a two-sided exact test. Baseline drug resistance mutations were observed in 90/546 (16.5%) patients: 56/90 (62.2%) with nonnucleoside analogue (NNRTI) mutations and 42/90 (46.6%) with nucleoside analogue mutations. In a stepwise, multiple regression analysis, the presence of the K103N mutation at initiation of therapy was associated with VF in both arms (p = 0.001), however, there was a higher incidence of VF in the stavudine arm compared to the emtricitabine arm regardless of the presence or absence of mutations at baseline (p = 0.001). In this study, the presence of drug-associated resistance mutations in ART-naive patients was significantly correlated with subsequent development of virologic failure underscoring the utility of testing for resistance in addition to the use of potent and well-tolerated first line regimens in treatment-naive patients.
authors.affiliation: Gilead Sciences, Inc., 4611 University Drive, Durham, North Carolina 27707, USA. kborrotoesoda@gilead.com
authors.forename: Katyna
authors.initials: K
authors.lastname: Borroto-Esoda
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Waters
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Bae
authors.forename: Jeanette L
authors.initials: JL
authors.lastname: Harris
authors.forename: John E
authors.initials: JE
authors.lastname: Hinkle
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Quinn
authors.forename: Frank S
authors.initials: FS
authors.lastname: Rousseau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016049:Didanosine / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D000068679:Emtricitabine; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D018119:Stavudine / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D003841:Deoxycytidine; D018119:Stavudine; D000068679:Emtricitabine; C098320:efavirenz; D016049:Didanosine