Study eases concerns over mental side effects from potent AIDS drug

The largest detailed, prospective clinical study of the mental side effects of a potent anti-AIDS drug, efavirenz, has revealed that the anxiety, dizziness, “funny feelings” and vivid dreams triggered by the drug fade away within a month, possibly clearing the way for more widespread use.

Sustiva is the brand name for the potent AIDS medication efavirenz.
Sustiva is the brand name for the potent AIDS medication efavirenz.

“Efavirenz is the first drug from its class that lasts long enough to be taken once a day, and that makes it a potentially valuable drug for AIDS treatment, ” says the study’s lead author, David Clifford, M.D., the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology and professor of medicine at Washington University School of Medicine in St. Louis.

Clifford and other scientists at Washington University’s AIDS Clinical Trials Unit (ACTU) studied 300 patients who were part of a larger multicenter trial. As a part of that other study’s protocol, patients were randomly and blindly taking either the anti-AIDS drug efavirenz or a placebo with alternative HIV therapy.

The findings were published in The Annals of Internal Medicine.

To keep the slippery, evasive virus that causes AIDS in check, patients take different types of drugs to impair or attack it on different fronts. Efavirenz was the first of a class of drugs known as non-nucleoside reverse transcriptase inhibitors that could be taken only once a day, a characteristic that substantially enhances the chances that patients will stick to the treatment regimen and keep the virus under control.

However, there have been lingering concerns over the mental side effects of efavirenz, which begin very soon after patients start taking the drug.

“Patients complain of ‘feeling funny’ or not feeling right almost with the first dose,” Clifford says. “Given that a chronic disorder such as AIDS is already likely to be associated with serious neuropsychiatric conditions including depression and anxiety, this was leading some physicians to shy away from prescribing efavirenz when they would prefer to see the patient taking the drug.”

Physicians and patients also were concerned about the potential for efavirenz’s mental side effects to impair performance when driving a car, operating machinery or doing other complex tasks.

David Clifford
David Clifford

Clifford and his colleagues at the ACTU developed a questionnaire to assess efavirenz’s effects on sleep and levels of depression and anxiety in a group evenly divided between patients taking efavirenz and patients taking a placebo. The patients took the survey one week, one month, three months and six months after they started treatment. They also took standardized tests of mental performance and response times.

“People who have a viral infection—think of the last time you had a bad case of the flu, for example—do suffer declines in brain function,” says Clifford. “Treatment reverses those declines, improving performance, and we found that both the patients who took efavirenz and those who didn’t had a similar improvement in performance that resulted from better suppression of HIV. Use of efavirenz was not associated with any decline in brain function.”

Results from the questionnaire revealed no difference in depression between the group taking efavirenz and the group taking a placebo.

The efavirenz group did have more anxiety, dizziness and vivid dreams after they began therapy, but those effects faded by the end of the first month.

“This drug really does do something in the brain, and we’ve had a very hard time determining how it causes these effects,” Clifford says. “But the important thing is that the effects wash out in the first month of using the drug. People now can be told that the chances are very good that if they just can stick with this drug for a few weeks they shouldn’t have ongoing problems.”

Clifford hopes to collaborate with inner ear researchers to get a better feel for how efavirenz might trigger dizziness in the first month of use. He also is continuing to give his questionnaire to patients in the study group as they continue to take efavirenz.

Clifford DB, Evans S, Yang Y, Acosta EP, Goodkin K, Tashima K, Simpson D, Dorfman D, Ribaudo H, Gulick RM. Impact of Efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Annals of Internal Medicine, November 15, 2005;143 (10): 714-721.

Funding from the National Institutes of Health supported this study.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.