title: HIV-1 amino acid changes among participants with virologic failure: associations with first-line efavirenz or atazanavir plus ritonavir and disease status.
abstract: BACKGROUND
  Although specific human immunodeficiency virus type 1 (HIV-1) drug resistance mutations are well studied, little is known about cumulative amino acid changes, or how regimen and participant characteristics influence these changes.
  
  
  METHODS
  In the AIDS Clinical Trials Group randomized study A5202 of treatment-naive HIV-infected participants, cumulative HIV-1 amino acid changes from pretreatment to virologic failure were evaluated in protease and reverse transcriptase (RT) gene sequences.
  
  
  RESULTS
  Among 265 participants with virologic failure, those assigned atazanavir plus ritonavir (ATV/r) did not have significantly more protease changes compared with those assigned efavirenz (EFV) (P ≥ .13). In contrast, participants with virologic failure assigned EFV had more RT changes, including and excluding known resistance codons (P < .001). At pretreatment, lower CD4 cell count, major resistance, more amino acid mixtures (all P < .001), hepatitis C antibody negativity (P = .05), and black race/ethnicity (P = .02) were associated with more HIV-1 amino acid changes.
  
  
  CONCLUSIONS
  Virologic failure following EFV-containing treatment was associated with more HIV-1 amino acid changes compared to failure of ATV/r-containing treatment. Furthermore, we show that non-drug resistance mutations occurred more frequently among those failing EFV, the clinical relevance of which warrants further investigation. Pretreatment immunologic status may play a role in viral evolution during treatment, as evidenced by increased amino acid changes among those with lower pretreatment CD4 count.
  
  
  BACKGROUND
  NCT00118898.
authors.affiliation: Harvard School of Public Health, Center for Biostatistics in AIDS Research, FXB Bldg, 651 Huntington Ave, Boston, MA 02115-6017, USA. kmollan@sdac.harvard.edu
authors.forename: Katie
authors.initials: K
authors.lastname: Mollan
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Maya
authors.initials: M
authors.lastname: Balamane
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Fischl
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lalama
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: David
authors.initials: D
authors.lastname: Katzenstein
mesh_terms: D000328:Adult; D000480:Alkynes; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000494:pharmacology* / Q000627:therapeutic use; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology* / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; C098320:efavirenz; D019438:Ritonavir