title: Human immunodeficiency virus type 1 protease genotype predicts immune and viral responses to combination therapy with protease inhibitors (PIs) in PI-naive patients.
abstract: Protease genotype, as a variable in outcome to combination therapy for human immunodeficiency virus (HIV) type 1 infection, was evaluated among protease inhibitor-naive children and adolescents who had received extensive treatment with reverse-transcriptase inhibitors. After 24 weeks of combination therapy, 35% had viral and immune success (VSIS patients), 19% had viral and immune failure (VFIF patients), and 46% had viral failure but marked improvement in CD4 T cells (VFIS patients). Disease stage was the only pretherapy clinical variable associated with outcome (P=.02). Although reverse-transcriptase genotype was unrelated to outcome, pretherapy protease genotype was related significantly to therapy response (P=.005). Odds for immune or viral failure were 17.7 to 1 and 2.5 to 1, respectively, for protease genotype as a single variable. Protease genotype combined with disease stage and CD4 cell percentage predicted correct therapy response for 81% of patients (100% of VFIF, 78% of VSIS, and 75% of VFIS patiens). Naturally occurring amino acid polymorphisms in protease provide sensitive biomarkers for treatment response among inhibitor-naive patients with advanced HIV disease.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Perez
authors.forename: S L
authors.initials: SL
authors.lastname: Rose
authors.forename: B
authors.initials: B
authors.lastname: Peyser
authors.forename: S L
authors.initials: SL
authors.lastname: Lamers
authors.forename: B
authors.initials: B
authors.lastname: Burkhardt
authors.forename: B M
authors.initials: BM
authors.lastname: Dunn
authors.forename: A D
authors.initials: AD
authors.lastname: Hutson
authors.forename: J W
authors.initials: JW
authors.lastname: Sleasman
authors.forename: M M
authors.initials: MM
authors.lastname: Goodenow
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D010802:Phylogeny; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease