HIV therapy is known to be associated with a large variability in efficacy and toxicity among different individuals even at standard doses. Reasons for this large inter-individual variability are attributed to race, gender, concomitant medications, drug compliance, underlying diseases, and genetic factors.
More than half of all medications including the majority of HIV medications are metabolized by three enzymes in the liver: CYP2D6, CYP2C9, and CYP2C19.[16] Other metabolizing pathways include CYP2B6, CYP3A4, HLA-B*57:01, SLCO1B1, and UGT1A1.
Population Frequency of Cytochrome P450 (CYP) Metabolizer Types [5]
| Poor (no or low enzyme levels) |
Intermediate (reduced enzyme levels) |
Extensive (normal enzyme levels) |
Rapid or Ultra Rapid Metabolizer (high enzyme levels) |
|
|---|---|---|---|---|
| CYP2D6* | 4-7% | 9-35% | 50-90% | 2-3% |
| CYP2C9 | 3% | 30% | 68% | N/A |
| CYP2C19* | 2-20% | 24-36% | 14-44% | 30% |
*CYP2C19 variability depends on ethnicity.
*CYP2D6 Variability depends on ethnicity and classification of Intermediate activity