Human immunodeficiency virus type 1 protease genotype predicts immune and viral responses to combination therapy with protease inhibitors (PIs) in PI-naive patients

Protease genotype, as a variable in outcome to combination therapy for huma n immunodeficiency virus (HIV) type 1 infection, was evaluated among protea se inhibitor-naive children and adolescents who had received extensive trea tment with reverse-transcriptase inhibitors. After 24 weeks of combination therapy, 35% had viral and immune success (VSIS patients), 19% had viral an d immune failure (VFIF patients), and 46% had viral failure but marked impr ovement in CD4 T cells (VFIS patients). Disease stage was the only prethera py clinical variable associated with outcome (P = .02). Although reverse-tr anscriptase 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 ge notype as a single variable. Protease genotype combined with disease stage and CD4 cell percentage predicted correct therapy response for 81% of patie nts (100% of VFIF, 78% of VSIS, and 75% of VFIS patients). Naturally occurr ing amino acid polymorphisms in protease provide sensitive biomarkers for t reatment response among inhibitor-naive patients with advanced HIV disease.