Neurological side-effects of efavirenz mild and transient, study claims

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HIV-positive patients taking efavirenz (Sustiva) tend to experience neurological side-effects such as bad dreams soon after starting treatment, but they usually resolve within the first four weeks of treatment. These findings were published in the 15th November edition of the Annals of Internal Medicine.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is commonly prescribed for HIV infection. The most commonly reported side-effects of the drug are neuropsychological, including bad dreams, dizziness, depression and anxiety. However, these reports have mostly come from studies where the participants knew which drugs they were taking.

To assess the incidence of these side-effects more accurately, investigators wished to monitor neuropsychological effects in a ‘blinded’ study in which the participants did not know which drugs they were taking.

Glossary

anxiety

A feeling of unease, such as worry or fear, which can be mild or severe. Anxiety disorders are conditions in which anxiety dominates a person’s life or is experienced in particular situations.

depression

A mental health problem causing long-lasting low mood that interferes with everyday life.

neurological

Relating to the brain or central nervous system.

open-label

A clinical trial where both the researcher and participants know who is taking the experimental treatment. 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

They carried out a sub-study of AIDS Clinical Trials Group study A5095, a three-arm randomised, controlled study that was designed to compare the effects of first-line HIV treatment with efavirenz, abacavir (Ziagen) and efavirenz plus abacavir. All three arms also took AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir).

“Transient, subjective neurologic effects are frequently experienced but are generally not severe,” they conclude. “Forewarned patients may safely continue the drug and anticipate that the symptoms will resolve promptly.

“Initiation of any therapy for HIV infection, together with the stresses of living with a serious chronic illness, requires careful patient monitoring and support, including recognition of substantial anxiety and depression,” they add. “Efavirenz, however, does not need to be avoided as a treatment for patients who are experiencing significant anxiety or depression.”

The investigators carried out a range of tests on the study participants, including neuropsychological tests questionnaires on their symptoms, assessments of sleep quality, anxiety and depression and blood levels of efavirenz.

Overall, neuropsychological symptoms improved in all of the patients, with no significant differences between the patients taking efavirenz and those who were not. The improvements were most dramatic in the first week of treatment.

However, when the results were broken down by symptom type, the investigators saw that the efavirenz group had more neurological symptoms at week 1 (p

The researchers also found that the patients taking efavirenz had more bad dreams during the first week of the study (p = 0.038). However, the significance of this finding is uncertain, since these patients had a marginally lower sleep quality score before the study began (p = 0.048). In addition, the patients taking efavirenz had better sleep quality at week 8 (p = 0.040). Sleep quality was unrelated to blood efavirenz levels.

Twelve (6%) of the 200 patients taking efavirenz stopped taking the drug before the end of the 24-week study due to effects on the central nervous system. In contrast, none of the 103 patients not taking efavirenz stopped for this reason.

In contrast to results from open-label studies, the investigators saw no differences between the groups in levels of anxiety or depression. “We provided a controlled, systematic evaluation of efavirenz on anxiety and depression and found no evidence that efavirenz-based regimens resulted in excess anxiety or depression,” the investigators write.

The investigators acknowledge that their study may be limited by patients with pre-existing neuropsychological symptoms being less likely to volunteer for the study. In addition, patients were allowed to switch from efavirenz to nevirapine (Viramune) if they experienced severe drug side-effects. The investigators analysed the effects of switching drugs in their study, finding that their conclusions were unaffected. However, they acknowledge that this could reduce the applicability of their findings.

References

Clifford DB et al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med 143: 714-721, 2005.