High levels of HIV drug cause mental problems

NEW YORK (Reuters Health) – 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.