HIV Digest	HIV Digest Archive

Although efavirenz (Sustiva) has been known to cause neuropsychiatric disturbances, studies to date have focused on the majority of patients for whom these symptoms are self-limited, rather than on the minority for whom they may continue unabated for months to years. While its one-pill once-a-day dosing makes it attractive from an adherence standpoint, potential adherence barriers, such as ongoing neuropsychiatric symptoms, need to be examined.

This cross-sectional comparative study from Bonaventura Clotet's group in Barcelona, interviewed 120 patients who had been on a stable efavirenz or a PI-based regimen for at least one year.

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Investigators recruited 120 patients, with no significant sociodemographic or clinical characteristic differences between arms. PI patients had been on the same regimen for a longer time and had a higher CD4+ cell count than the efavirenz group. The percentage of patients who had a CD4+ cell count of less than 200 was similar. The most used PI was nelfinavir (NFV, Viracept).

Fifty-four percent of patients in the efavirenz group and 27% in the PI group reported at least one neuropsychiatric disorder within a month prior to the visit. The efavirenz group reported a statistically significantly higher prevalence of dizziness, sadness, mood changes, irritability, lightheadedness, nervousness, impaired concentration, abnormal dreams and somnolence. Mean efavirenz levels were not significantly different between subjects with and without neuropsychiatric symptoms and high plasma levels of efavirenz were not associated with symptoms.

There were no significant differences between groups regarding quality of life. The median POMS-A score was 4 in the efavirenz group and 3 in the PI group with no differences on any of the subscales. Comparison with regard to the other psychological variables was not different between groups.

Sixty percent of efavirenz patients and 55% of PI patients reported more than 95% adherence. In univariate analysis, age, lack of substance abuse and effort to follow the treatment schedule were associated with adherence. An inverse relationship between time on treatment and adherence was observed, with adherence decreasing over time on treatment. In multivariate analysis, only lack of substance abuse and effort to follow the treatment schedule were predictors of adherence more than 95%.

While over half of the efavirenz patients had persistent neuropsychiatric symptoms on long-term therapy (mean of 91.1 weeks on an efavirenz-based regimen), these symptoms were usually mild and clinically tolerable. More than half of the patients were employed and able to maintain an active life. As has been reported in past studies, abnormal dreams, sadness, irritability, nervousness, lightheadedness and difficulty in sleeping were the most frequent adverse events in the efavirenz group, with the statistically significant increase in these symptoms in the efavirenz group, leading the investigators to surmise that this drug was playing a key role.

While previous researchers have found a correlation between high efavirenz levels and central nervous system (CNS) symptoms, none was found here, perhaps because patients who had high levels had already discontinued therapy due to the symptoms. An important caveat to this study is that patients who had mental health histories that included depression were excluded from participating. Thus these results may not be reflective of the full range of patients for whom this drug is prescribed. However, the persistence of symptoms at almost two years of follow-up in over half of the efavirenz patients is a key finding and one that bears remembering in day-to-day clinical practice.

Editor's Note: from theBodyPro.com