Neuropsychological Side Effects of Efavirenz

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The summary below is from the full report titled "Impact of Efavirenz on Neuropsychological Performance and Symptoms in HIV-Infected Individuals." It is in the 15 November 2005 issue of Annals of Internal Medicine (volume 143, pages 714-721). The authors are D. Clifford, S. Evans, Y. Yang, E.P. Acosta, K. Goodkin, K. Tashima, D. Simpson, D. Dorfman, H. Ribaudo, and R.M. Gulick for the A5097s Study Team.

What is the problem and what is known about it so far?

Infection with the HIV-1 virus is a serious chronic illness. The virus attacks key cells of the body's immune system and interferes with its ability to fight infection and certain types of cancer. Multiple drugs can successfully suppress the virus and improve the immune function of cells. One of these drugs is efavirenz. It is a drug (a nonnucleoside reverse transciptase inhibitor) that works by impairing the virus' ability to multiply.

Like any drug, efavirenz causes side effects. Some of the most bothersome are neurologic or psychological problems. These include insomnia and bad dreams, thinking problems and poor concentration, memory loss and loss of identity, anxiety and depression, dizziness, and confusion and hallucinations. Some research shows that more than 50% of patients taking efavirenz experience one or more of these side effects. We do not know much about the severity of the side effects or if they get better over time.

Why did the researchers do this particular study?

To find out the types, severity, and duration of neuropsychological side effects that are caused by efavirenz.

Who was studied?

303 HIV-1–infected adults who had participated in a larger randomized trial that had compared multiple antiviral treatments.

How was the study done?

For the original trial, the researchers recruited patients with detectable virus (HIV-1 RNA levels greater 400 copies/mL) who had not received any prior antiretroviral therapy. The researchers gave all patients 2 antiviral drugs (zidovudine and lamivudine). They also randomly assigned patients to receive one of 3 additional therapies (efavirenz alone, abacavir alone, or abacavir and efavirenz together). To ensure that the researchers and the patients would know who received which treatment, they gave dummy pills (placebos) to patients assigned to efavirenz or abacavir. In this substudy, the researchers compared neuropsychological symptoms and test results of patients assigned to receive efavirenz with those of patients assigned to receive abacavir and placebo. The tests measured cognition, thinking ability, sleep experience, anxiety, and depression. They were given to patients 1, 4, 12, and 24 weeks after starting therapy.

What did the researchers find?

Of 200 HIV-infected adults, 12 (6%) stopped taking efavirenz because of neurologic symptoms or mood disorders. None of the 103 adults in the group receiving abacavir and the placebo pill discontinued therapy because of neurologic symptoms or mood disorders. Adults taking efavirenz had more symptoms, including sleep problems and bad dreams in the first week of treatment. Most patients (>80%) in both groups had anxiety throughout the study. No major differences in anxiety, depression, sleep experience, cognitive performance, or symptoms were seen between groups at 4, 12, and 24 weeks.

What were the limitations of the study?

The study did not examine all types of side effects that might occur with efavirenz. Other commonly reported side effects include a blister-type rash, nausea, vomiting, and diarrhea. The study used only a few measures of neurologic function. These tests may have missed some problems.

What are the implications of the study?

Efavirenz causes neuropsychological side effects such as bad dreams. Many of these side effects are temporary and, if caused by efavirenz, might resolve within a few weeks.