title: Suboptimal etravirine activity is common during failure of nevirapine-based combination antiretroviral therapy in a cohort infected with non-B subtype HIV-1.
abstract: OBJECTIVE
  The primary objective of this study was to estimate etravirine activity in a cohort of patients infected with non-B subtype HIV-1 and failing nevirapine-based therapy.
  
  
  METHODS
  Genotypic resistance testing was performed if viral load was >OR= 1,000 copies/ml after receiving at least six months of therapy. Suboptimal response to etravirine was predicted by a score >OR= 2.5 on the Tibotec weighting schema, >OR= 4 in the Monogram schema, or classification as high to low-level resistant by a modification of the Stanford HIVdb algorithm (Version 5.1.2). Bivariate and multivariate analyses were conducted to determine the risk factors for suboptimal etravirine activity.
  
  
  RESULTS
  The patients (n=91) were receiving nevirapine and lamivudine plus stavudine (57.1%) or zidovudine (42.9%). Median duration of nevirapine exposure was 53 weeks (IQR 46-101 weeks). The most common etravirine resistance associated mutations were Y181C (42.9%), G190A (25.3%), H221Y (19.8%), A98G (18.7%), K101E (16.5%), and V90I (12.1%). Suboptimal etravirine activity was predicted in 47.3 to 56.0%. There were disparities in mutations listed in Tibotec versus Monogram Schemas. Predicted suboptimal activity was not associated with nucleoside reverse transcriptase inhibitor (NRTI) used, gender, pretreatment or current CD4 cell count or viral load, subtype or NRTI mutations.
  
  
  CONCLUSIONS
  Etravirine has compromised activity in approximately half of the patients failing nevirapine-based first-line treatment in this cohort, which supports guidelines that caution against using it with NRTIs alone in such patients.
authors.affiliation: Northwestern University Feinberg School of Medicine, Infectious Diseases Division, Chicago, IL 60611, USA. b-taiwo@northwestern.edu
authors.forename: Babafemi
authors.initials: B
authors.lastname: Taiwo
authors.forename: Beth
authors.initials: B
authors.lastname: Chaplin
authors.forename: Sudhir
authors.initials: S
authors.lastname: Penugonda
authors.forename: Seema
authors.initials: S
authors.lastname: Meloni
authors.forename: Sulaimon
authors.initials: S
authors.lastname: Akanmu
authors.forename: Wadzani
authors.initials: W
authors.lastname: Gashau
authors.forename: John
authors.initials: J
authors.lastname: Idoko
authors.forename: Isaac
authors.initials: I
authors.lastname: Adewole
authors.forename: Robert
authors.initials: R
authors.lastname: Murphy
authors.forename: Phyllis
authors.initials: P
authors.lastname: Kanki
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use*; D009570:Nitriles; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines; D017211:Treatment Failure; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D014764:Viral Proteins; C451734:etravirine; D019829:Nevirapine