Long-Term Efficacy and Safety of Efavirenz Dose Reduction to 200 mg Once Daily in a Caucasian Patient with HIV

A 48-year-old Caucasian male patient presented with severe adverse drug events (ADEs) while being treated with a standard dose (600 mg/day) of efavirenz. The patient's clinical course was favourable; however, he also described intense nightmares, cramps in his legs and anxiety disturbances that made him highly irritable. Measurement of the patient's efavirenz plasma concentrations revealed a mean minimum steady-state concentration during a dosage interval (C min,ss) of 12.7 mg/L, which was much higher than that recommended for this drug (therapeutic range 1-4 mg/L). Consequently, the dose of efavirenz was reduced to 400 mg/day, which resulted in a decrease in the frequency of ADEs. Subsequent genotype testing showed that the patient was homozygous for both the CYP2B6-G516T (T/T) and CYP2B6-A785G (G/G) alleles; these polymorphisms are associated with reduced enzymatic activity and elevated efavirenz plasma concentrations. Because of this and the fact that the patient's mean efavirenz C min,ss was still high (4.6 mg/L), a second dosage reduction was undertaken, to 200 mg/day. This also resulted in a reduction in ADEs. At present, the patient's CD4+ levels remain stable, his viral load continues to be undetectable and the mean efavirenz Cmin,ss is within the therapeutic range (2.7 mg/L). [PUBLICATION ABSTRACT]