High Levels of HIV Drug Cause Mental Problems

In Spain, researchers studying long-term efavirenz therapy found that patients at higher doses had an increased rate of adverse psychiatric events, new research suggests.

Up to half of patients on long-term efavirenz therapy may experience mental disorders, but data are lacking on which patients are at risk, noted Felix Gutierrez, of the Hospital General Universitario de Elche in Alicante, and colleagues.

Researchers evaluated 17 patients on efavirenz-containing regimens who had no history of mental illness. They assessed patients every three months for 18 months, and they tested efavirenz levels five times.

Ten patients experienced mental issues during the study, with sleeping problems being the most common. In four patients, moderate to severe side effects included depression (two patients), mood and concentration/attention problems (one) and obsessive disorder (one). All four discontinued efavirenz.

Patients' efavirenz blood levels ranged from 0.62 to 12.59 micrograms/milliliter, with a 2.74 level being highly predictive for mental disturbances, researchers found. Patients with efavirenz blood levels above 2.74 micrograms/milliliter had a five-fold greater risk of central nervous system side effects than other patients.

Studies have shown efavirenz levels above 1 microgram/milliliter may be adequate to suppress HIV, so "there may be room for dose reduction to avoid [side effects] in selected cases," wrote authors. However, patients in whom other regimens have failed may require blood levels above 3 micrograms/milliliter, they added.

"Future studies are needed to assess whether therapeutic drug monitoring will result in a decrease in the percentage of patients developing [mental problems] while receiving efavirenz-containing regimens with no loss of efficacy," the authors reported.

The full study, "Prediction of Neuropsychiatric Adverse Events Associated with Long-Term Efavirenz Therapy, Using Plasma Drug Level Monitoring," was published in Clinical Infectious Diseases (2005;41:1648-1653).

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