Higher blood levels of the anti-HIV drug efavirenz confer an increased risk of mental problems, Spanish researchers report.

Patients with blood levels above 2.74 micrograms/milliliter were at more than five-fold greater risk of central nervous system side effects than other patients, Dr. Felix Gutierrez of the Hospital General Universitario de Elche in Alicante and colleagues report.

New research suggests as many as half of patients on long-term efavirenz may develop mental disorders, but there is little information on which patients are at risk, Gutierrez and his team note in Clinical Infectious Diseases.

To investigate whether monitoring blood levels of the drug could predict central nervous system side effects, the researchers followed 17 patients taking drug combinations containing efavirenz. None had a history of mental illness.

Participants were evaluated at the beginning of the study and every three months for a total of 18 months, while efavirenz levels were measured five times.

Ten of the patients reported mental issues during the study, with sleep problems being the most common. Moderate or severe side effects occurred in four of the patients - two had depression, one had changes in mood and concentration and attention problems, and one developed obsessive disorder. All four discontinued the drug.

Patients’ blood levels ranged from 0.62 to 12.59 micrograms/mL. The cutoff point of 2.74 micrograms/mL was highly accurate in predicting mental disturbances, the researchers found.

Past research has shown a blood level of efavirenz greater than 1 microgram/milliliter may be enough to suppress HIV, suggesting “there may be room for dose reduction to avoid (side effects) in selected cases,” Gutierrez and his colleagues write. However, they add, blood levels above 3 micrograms/milliliter may be necessary in patients who have failed treatment with other drugs.

“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 state.

SOURCE: Clinical Infectious Diseases, December 1, 2005.