No evidence that patients taking long-term efavirenz want to switch to etravirine

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Patients who are on long-term efavirenz therapy do not prefer etravirine after switching to this drug, Swiss investigators report in the online edition of AIDS. Switching to etravirine was not associated with any improvements in sleep quality or mood.

“Multiple, validated questionnaires did not confirm a benefit from etravirine over efavirenz regarding anxiety, depression or quality of sleep. Accordingly, patients did not express a significant preference for etravirine over efavirenz,” comment the researchers.

Efavirenz (Sustiva, also in the combination pill Atripla) is a highly effective and widely used anti-HIV drug from the non-nucleoside reverse transcriptase inhibitor (NNRTI) class.

Glossary

lipid

Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

depression

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

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.

It is generally very safe, but in some studies as many as 50% of patients have reported sleep and mood problems in the early weeks of treatment with the drug.

These symptoms usually lessen or go away completely, but a minority of patients are unable to tolerate efavirenz and therefore switch to an alternative drug.

Etravirine (Intelence) is a new potent NNRTI. Its main side-effect is rash, and there is no evidence that it causes sleep or mood disturbances.

Swiss investigators hypothesised that some patients taking long-term efavirenz therapy would have sub-clinical neuropsychological problems that would improve after their treatment was switched to etravirine.

They therefore designed a twelve-week cross-over study involving 58 patients. All the patients had an undetectable viral load and had been taking efavirenz for at least three months. It was not a requirement to have efavirenz-associated neuropsychiatric symptoms to be included in the study.

The patients were randomised into two groups. For six weeks, half continued to take efavirenz and were also given an etravirine placebo. The other patients were switched to etravirine and took an efavirenz placebo. After six weeks, both groups changed to the alternative combination.

Questionnaires were administered that enquired about the participants’ mood and sleep patterns, and the end of the study the patients were asked if they preferred the treatment they received during the first six weeks, or the second six weeks of the study.

Lipid levels were also monitored.

Most (87%) of the participants were men, and their median age was 47. They had well-controlled HIV, and the median CD4 cell count was 589 cells/mm3. The patients had been taking efavirenz for an average of 3.9 years.

Results showed that 16 patients preferred efavirenz, 22 etravirine and 17 did not have a preference. These differences were not significant.

However, the investigators found that patients had a preference for the drug that they took first.

Of those who took efavirenz first, 71% said that they preferred it, and 94% of patients who took etravirine first said that they favoured this drug. “We assume that this was due to the recrudescence of symptoms when efavirenz was restarted”, comment the investigators.

There was no real difference in levels of satisfaction with the two drugs. A total of 32 individuals reported satisfaction with etravirine, nine were neutral and 13 were dissatisfied. In all, 23 patients said that they were satisfied with efavirenz, 15 were neutral and 17 were dissatisfied. There differences were not significant.

At the end of the study when the medications were unblinded, 35 individuals chose to continue to take efavirenz and 20 opted to switch to etravirine. Once again, individuals had a preference for the drug they took first.

Reported sleep quality, as well as levels of depression, anxiety, and drowsiness, were comparable between the two drugs.

However, lipid profiles improved when the patients were taking etravirine. Total cholesterol (p < 0.0001), LDL-cholesterol (p < 0.0001), and triglycerides (p = 0.0002) all fell significantly when the patients switched to etravirine.

The researchers comment “our results indicate that etravirine may represent an interesting therapeutic option for patients with lipid abnormalities.” However, they conclude, “patients on long-term efavirenz do not, as a rule, prefer etravirine after a switch.”