Japanese researchers have found that some people can safely reduce their dose of Sustiva (efavirenz) and possibly reduce the chance of side effects. The article, which appears in the November 1 issue of Clinical Infectious Diseases, reveals that certain genetic mutations to a key liver enzyme can result in blood levels of Sustiva that are much higher than normal, and people with these mutations can benefit from a dose reduction.
A team headed by Hiroyuki Gatanaga, MD, of the International Medical Center of Japan in Tokyo enrolled 456 people who were currently taking Sustiva or about to start it. They tested the participants for genetic mutations to a liver enzyme called CYP2B6, which had been shown to affect Sustiva blood concentrations. Genetic mutations can be inherited from one or both parents. Typically, when someone inherits such a mutation from both parents its effect is stronger. Researchers identified 18 people who had inherited the mutation from both parents, and all of them had extremely high blood concentrations of Sustiva. Researchers were able to reduce the dose of Sustiva from the standard dose of 600mg to 400mg in 11 people and to 200mg in 7 people without sacrificing control of the virus.
Of the 18 people who experimented with a dose reduction, 14 had complained of dizziness and sleep disturbance at the higher dose of Sustiva. After reducing the dose of Sustiva, all 14 reported that their dizziness went away. However, all of them still reported some degree of sleep disturbance. Further research is needed to determine how common the mutations are among people with HIV, to validate the tests that look for them, and to determine whether Sustiva dose reductions are safe in a large number of patients.
