Switch from efavirenz to raltegravir improves mood and lipid profiles

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.

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.