Genotype and phenotype of cytochrome P-450 2D6 in human immunodeficiency virus-positive patients and patients with acquired immunodeficiency syndrome

Objective: To examine the distribution of the cytochrome P-450 (CYP) CYP2D6 phenotype and its relation to genotype, concomitant medication, and diseas e state in human immunodeficiency virus (HIV)positive patients. Design: A cross sectional study with a longitudinal component compared indi vidual genotypes for CYP2D6 to the CYP2D6 phenotype. Methods: Sixty-one predominately male Caucasian, HIV-positive patients were recruited and CYP2D6 genotypes [extensive metabolizer (EM) or poor metabol izer (PM)] determined by polymerase chain reaction (PCR)-based amplificatio n, followed by restriction fragment-length analysis. The patients were also phenotyped using dextromethorphan (DM) to determine their respective enzym e activity and assigned either a CYP2D6 EM or PM phenotype. Complete medica l and treatment histories were compiled. A total of 44 patients were tested longitudinally. Results: Fifty-nine patients (97%) possessed an EM genotype, consistent wit h previously observed distributions in demographically similar populations. In healthy seronegative populations, genotype and phenotype have been show n to be essentially interchangeable measures of CYP2D6 activity. In this co hort, 2 of the 59 patients with an EM genotype expressed a PM phenotype. In addition, 4 EM patients were less extensive DM metabolizers than any of th e patients receiving medication known to inhibit CYP2D6. This apparent shif t toward the PM phenotype from the EM genotype was associated with the pres ence of active illness. Conclusion: Changes may occur in HIV-positive patients such that their CYP2 D6 activity approaches that of PMs, despite having an EM genotype. Neither active disease nor drug interactions alone explain the shift.