Switch from efavirenz to raltegravir improves mood and lipid profiles

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Switching from efavirenz (Sustiva) to raltegravir (Isentress) is associated with improvements in mood and lipid profiles, Swiss investigators report in the online edition of AIDS.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and is widely used in first-line HIV therapy.

The drug is associated with good outcomes and is generally considered safe. However, it can cause neuropsychiatric side-effects, including depression, anxiety, and sleep problems.



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.


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.


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).


A clinical trial where neither the researchers nor participants know which assigned treatment an individual participant in the trial is taking until after the end of the trial. This reduces the risk of biased results. 


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

These are most likely to occur during the first few weeks of therapy with the drug. For some patients, however, they are a subtle, long-term problem. Moreover, efavirenz has also been associated with disturbances in cholesterol and triglycerides. 

Raltegravir is a recently licensed HIV integrase inhibitor, and there is no evidence that the drug causes the mood and sleep disorders associated with efavirenz. Therefore researchers wanted to investigate the effect of replacing efavirenz with raltegravir on patient preference, mood and sleep, and lipid profiles.

Their study involved patients who were taking long-term efavirenz-based therapy, and had a randomised, double-blind, cross-over design.

A total of 57 patients were randomised and 53 completed the four-week study.

Patients in the first arm received raltegravir plus an efavirenz placebo; individuals in the second arm were given efavirenz and a raltegravir placebo. After two weeks, they switched therapy which they continued for a further 14 days.

All the patients continued to take their NRTI backbone.

Patient preference, mood and sleep were assessed using questionnaires. Blood samples were taken at baseline, and again at week two and week four to assess the impact of therapy on lipids.

All the patients had an undetectable viral load, and their median CD4 cell count was 600 cells/mm3. The average duration of efavirenz therapy was 3.4 years.

At the end of the study, 64% of patients expressed a preference for treatment in one of the study phases.

Their answers showed that 65% of patients preferred raltegravir and 35% had a preference for efavirenz. At the end of the study, 51% of patients switched from efavirenz to raltegravir.

Patient satisfaction with treatment was significantly higher during the raltegravir phase of the study (p = 0.002).

Raltegravir was also associated with significantly better stress (p = 0.03) and anxiety scores (p = 0.04).

In addition, therapy with raltegravir was associated with significantly lower total cholesterol (p < 0.001) and LDL cholesterol (p = 0.036).

“Approximately half of patients previously stable on efavirenz preferred to switch to raltegravir, after double-blind exposure to raltegravir for two weeks,” comment the investigators.

They believe this high rate of treatment change could indicate that low-level mood disorders are present in a many patients taking long-term efavirenz treatment.

“Switching to raltegravir was associated with significant improvements in anxiety and stress…and improvement in lipid profile,” conclude the authors.


Nguyen A et al. A randomized cross-over study to compare raltegravir and efavirenz (SWITCH-ER) study. AIDS 25 online edition: doi: 10. 1097/QAD.0b013e328348dab0, 2011 (click here for the free abstract).