March 12, 2009

Low-Dose Efavirenz Safe for Some

Efavirenz (found in Sustiva and Atripla) may be safe and effective at one third the standard dose in some people, according to a research letter published January 28 in AIDS and reported by aidsmap. Specifically for HIV-positive people with a key genetic characteristic, lowering the dose may completely resolve the pesky central nervous system (CNS) side effects of efavirenz.

In AIDS Clinical Trials Group (ACTG) study 5095, a study completed several years ago, it was noted that people with a genetic variation (a polymorphism) in CYP2B6—a member of a group of enzymes responsible for breaking down some drugs, including efavirenz, in the body—had higher blood levels of efavirenz than people without the polymorphism. Researchers from ACTG 5095 estimated that roughly 3 percent of white and 20 percent of black patients may have the polymorphism, known as CYP2B6 G516T. The study, however, did not find a consistent link between the higher efavirenz blood levels and worse CNS side effects.

Further research to determine the clinical significance of testing for the polymorphism languished due to concerns about the expense of such a test. Now, however, Hiroyuki Gatanaga, MD, and Shinichi Oka, MD, of the AIDS Clinical Center at the International Medical Center in Tokyo write that a Japanese laboratory has developed a CYP2B6 G516T test that would cost about $75.

In a small study conducted by Gatanaga and Oka, 12 people with the polymorphism and high blood levels of efavirenz had their dose of the drug reduced—in five people to 400 milligrams per day and seven people to 200 mg per day. The standard dose of efavirenz is 600 mg a day. After reducing the dose, all of the nine people who had previously reported chronic CNS side effects—such as vivid dreams, muddled thinking and emotional difficulties—saw their side effects resolve completely. All of the patients have also been able to keep their viral loads below the level of detection using the lower dose of efavirenz.

The authors describe how the study affected one of their patients, a 71-year-old man who had nightmares every night until his dose was reduced. They first lowered his dose to 400 mg, and then ultimately 200 mg, wherein his nightmares completely stopped. He has now gone for two years on the lower dose of efavirenz and maintained a viral load of less than 50 copies.

Though the genetic polymorphism is not common, Gatanaga and Oka argue that the potential savings from using a lower dose of efavirenz, along with the potential benefit in terms of reduced side effects, justify a larger study to confirm that such testing is both safe and feasible.

Search: Efavirenz, Sustiva, Atripla, dose reduction, CYP2B6, CYP2B6 G516T, Hiroyuki Gatanaga, Shinichi Oki

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