title: Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy.
abstract: BACKGROUND
  Study GS-01-934 was a randomized open-label phase III study comparing efavirenz and tenofovir/emtricitabine to efavirenz and zidovudine/lamivudine in treatment-naive HIV-1-infected individuals. Through 144 weeks, 50 of 487 participants without baseline nonnucleoside reverse transcriptase inhibitor resistance by population sequencing (efavirenz/tenofovir/emtricitabine, n = 19; efavirenz/zidovudine/lamivudine, n = 31) experienced virologic failure (>400 copies/ml). Here, we analyzed whether the presence of low levels of K103N at baseline correlated with virologic failure.
  
  
  METHODS
  Available baseline plasma samples (n = 485) were amplified and tested for K103N using an allele-specific PCR (AS-PCR) assay with a lower detection cut-off of 0.5%.
  
  
  RESULTS
  Sixteen of 476 (3.4%) evaluable participants had low-level K103N at baseline by AS-PCR (0.8-15%). The abundance of the K103N subpopulation at baseline distinguished individuals with virologic failure from those who responded durably to efavirenz-containing therapy. Among six participants with at least 2000 K103N copies/ml before treatment, five experienced virologic failure, compared with only one virologic failure among 10 who had less than 2000 K103N copies/ml (P = 0.008). Multivariate logistic regression analysis showed that K103N viral load at least 2000 copies/ml increased the risk of virologic failure with an odds ratio of 47.4 (95% confidence interval 5.2-429.2, P = 0.0006).
  
  
  CONCLUSIONS
  The presence of K103N mutant virus in plasma above 2000 copies/ml prior to therapy in treatment-naive individuals correlated with increased risk of virologic failure of these efavirenz-containing triple-drug regimens.
authors.affiliation: Gilead Sciences Inc., Durham, North Carolina, USA.
authors.forename: Derrick D
authors.initials: DD
authors.lastname: Goodman
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Margot
authors.forename: Damian J
authors.initials: DJ
authors.lastname: McColl
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhong
authors.forename: Katyna
authors.initials: K
authors.lastname: Borroto-Esoda
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Evguenia S
authors.initials: ES
authors.lastname: Svarovskaia
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000008:administration & dosage* / Q000494:pharmacology; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D012367:RNA, Viral / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D012367:RNA, Viral; D003841:Deoxycytidine; D019259:Lamivudine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C098320:efavirenz