High blood concentrations of efavirenz associated with poor sleep

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High blood concentrations of efavirenz (SustivaTM) are correlated with poor sleep, according to a Spanish study published to be published in the February 1st edition of Clinical Infectious Diseases, which is now available online.

The investigators also found that patients taking efavirenz with sleep problems were more likely than HIV-positive individuals taking the drug with normal sleep or HIV-negative volunteers to have reduced sleep efficiency, to spend more time awake during the night, to have less REM sleep, and to wake up more often during the night.

Investigators recruited 18 HIV-positive patients taking efavirenz to the study. These individuals were diagnosed with sleep disturbance after completing a sleep diary. The study also involved 13 HIV-negative controls.





The fluid portion of the blood.

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 


The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 


How well something works (in a research study). See also ‘effectiveness’.

Sleep was assessed using electroenencephalogram monitoring and the HIV-positive patients had their plasma efavirenz levels monitored in the morning, twelve hours after taking their daily bedtime dose.

The HIV-positive patients and controls were closely matched as regards age and sex, and at the time of sleep assessment, the HIV-positive patients had a mean CD4 cell count of 424 cells/mm3, median viral load was 90 copies/mL, and the mean duration of efavirenz treatment was six months.

Individuals with efavirenz-related insomnia had low sleep values (mean 81%) compared to normal sleep value in the either efavirenz-treated patients with without insomnia or healthy volunteers (above 90% sleep avalue). Individuals taking efavirenz with sleep problems spent more time awake during the night than, mainly due to higher frequency of night arousals than either the efavirenz-treated patients without insomnia or the healthy volunteers (4.1 versus 2.6 versus 2.1).

Poor efavirenz sleepers were also significantly more likely to have difficulty falling asleep (sleep latency mean 30.9 minutes versus 10.9 minutes healthy volunteers). To compensate for poor nighttime sleep, individuals with efavirenz-related sleep disturbance spent more time napping during the day (mean 32.5 minutes versus 12.1 minutes efavirenz-treated with no insomnia and 10.3 minutes healthy volunteers).

Patients with insomnia also had less rapid eye movement (REM) sleep than healthy volunteers (mean 14% versus 22.6% for both other groups, P<0.05), and less non-REM deep sleep (mean 9.1% versus 21.6% healthy volunteers, p<0.05).

Among HIV-positive patients with insomnia, efavirenz concentrations had higher concentrations of efavirenz (4.3mg/L versus 2.7mg/mL), but this difference did not reach statistical significance. However, sleep efficiency below 90% was almost twice as common in individuals with plasma concentrations of efavirenz of 4mg/L or above (62.5% versus 37.5%, p=0.04).

The investigators conclude “the observance that plasma efavirenz levels correlate with reductions in sleep efficiency opens a door to investigate whether adjusting efavirenz dosages could ameliorate sleep disturbances without compromising the drug’s virologic efficacy.?

Further information on this website

Efavirenz - overview

Sleep - factsheet


Gallego L et al. Analyzing sleep abnormalities in HIV-infected patients treated with efavirenz. Clinical Infectious Diseases 38 (on-line edition), 2004.