title: Impact of minority nonnucleoside reverse transcriptase inhibitor resistance mutations on resistance genotype after virologic failure.
abstract: Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants increase the risk of virologic failure for first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. We performed a pooled analysis to evaluate the relationship between NNRTI-resistant minority variants and the likelihood and types of resistance mutations detected at virologic failure. In multivariable logistic regression analysis, higher NNRTI minority variant copy numbers, non-white race, and nevirapine use were associated with a higher risk of NNRTI resistance at virologic failure. Among participants on efavirenz, K103N was the most frequently observed resistance mutation at virologic failure regardless of the baseline minority variant. However, the presence of baseline Y181C minority variant was associated with a higher probability of Y181C detection after virologic failure. NNRTI regimen choice and preexisting NNRTI-resistant minority variants were both associated with the probability and type of resistance mutations detected after virologic failure.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. jli22@partners.org
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Li
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kozal
authors.forename: Evguenia S
authors.initials: ES
authors.lastname: Svarovskaia
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Geretti
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Metzner
authors.forename: Martin R
authors.initials: MR
authors.lastname: Jakobsen
authors.forename: Katherine Huppler
authors.initials: KH
authors.lastname: Hullsiek
authors.forename: Lars
authors.initials: L
authors.lastname: Ostergaard
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000208:ethnology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz