A significant number of patients taking efavirenz (Sustiva) as a component of their antiretroviral therapy experience chronic neuropsychiatric symptoms, according to a small Australian study published in the November edition of HIV Medicine. Neuropsychiatric side-effects are commonly regarded as a short-term toxicity of efavirenz therapy, but the patients in the study had been taking the drug for at least six months, and were compared with comparable patients taking long-term HIV therapy that did not include efavirenz.
Approximately 50% of patients starting therapy with efavirenz develop neuropsychiatric side-effects in the first two weeks of treatment with the drug, and earlier studies have shown that up to 13% of individuals stop treatment with the drug at this time because of such toxicities. Generally, central nervous system (CNS) side-effects develop after taking the first dose of efavirenz, but tend to disappear after a month of treatment. There is concern that a number of patients experience longer-term efavirenz-related CNS side-effects and that between 4% - 10% of patients treated with the drug discontinue its therapy because of chronic CNS side-effects.
Investigators in Sydney, Australia wished to determine the prevalence of long-term CNS side-effects in patients taking efavirenz as part of a stable antiretroviral regimen. They therefore conducted a cross-sectional, case-controlled study that matched individuals taking long-term (over six months) efavirenz with comparable HIV-positive individuals taking a long term antiretroviral combination that did not include this drug. The investigators also used validated questionnaires to assess CNS symptoms experienced by patients in the study: the Depression Anxiety and Stress Scale (DASS); and the Cognitive Failures Questionnaire (CFQ), a tool to assess forgetfulness and aggression in daily life. The investigators also developed their own questionnaire to assess sleep disturbance, a commonly reported side-effect of efavirenz.
A total of 32 matched pairs were included in the investigators’ analysis. Although the pairs were generally comparable, patients taking non-efavirenz regimens had been taking their current treatment for longer (mean 24 months versus 14 months, p = 0.001).
Patients taking efavirenz reported higher levels of stress (p = 0.008), and there was a non-significant trend for patients treated with efavirenz to report more depression (p = 0.077), and anxiety (p = 0.083).
However, 19% of patients taking efavirenz reported “severe stress” compared to none of the individuals taking other regimens, a difference that was statistically significant (p = 0.014). Furthermore, 19% of patients treated with efavirenz experienced “severe to extremely severe” anxiety compared to only 3% of patients taking regimens that did not include this drug, and once again this difference was statistically significant (p = 0.05). There was also a trend for patients taking efavirenz to report “severe or extremely severe” depression (p = 0.083).
Further analysis of the stress scores showed that patients taking efavirenz had had more difficulty relaxing (p = 0.0029), became easily upset or agitated (p = 0.025), and were more likely to report being irritable or overactive (p = 0.009).
A significantly higher proportion of the efavirenz-treated patients reported unusual dreams in the last seven days (58% versus 32, p = 0.049), but quality of sleep was comparable between the two groups of patients.
The investigators performed a second set of analyses because patients who were not taking efavirenz had been on their treatment for longer. But this did not affect the findings of their study.
The study’s investigators state that that is of “paramount” importance to find the clinical features associated with these side-effects so that clinicians can develop “improved management strategies”.
Rihs TA et al. Efavirenz and chronic neuropsychiatric symptoms: a cross-sectional case control study. HIV Med 7: 544 – 548, 2006.