Background: Insomnia is frequently found in patients (pts) receiving efavirenz (EFV). It generally resolves within the first month on treatment, although eventually may lead to EFV discontinuation. Information on the sleep pattern alterations induced by EFV and their potential association with EFV plasma levels is scarce.

Methods: A total of 18 HIV⁺ subjects receiving EFV for at least 1 month, and a control group of 13 healthy volunteers were recruited in the study. Insomnia was assessed through sleep diaries and the Pittsburgh Sleep Quality Index (PSQI) and psychiatric screening ruled out other mental co-morbidities. Ambulatory (Holter) EEG monitoring was used to record sleep architecture in HIV⁺ and healthy controls. EFV plasma trough levels were measured in HIV⁺ pts.

Results: Sleep diaries and the PSQI identified insomnia in 13 subjects receiving EFV, while normal results were obtained in the remaining 5 HIV⁺ pts on EFV and in all 13 healthy controls. In comparison with subjects without sleep disturbances, pts with EFV-related insomnia showed lower sleep efficacy (81 ±15% vs 96 ±7%, p < 0.01), longer total time awake (20 ±15% vs 4 ±0.2%, p < 0.01), shorter REM (14 ±6% vs 22 ±3%, p < 0.01), and shorter NREM stage 2 (43 ±6% vs 56 ±7%, p < 0.01) in the ambulatory EEG monitoring. Conversely, HIV⁺ pts on EFV, irrespectively of suffering insomnia, showed longer sleep latencies than healthy controls (32 ±28 mins vs 11 ±3 mins, p < 0.01), and shorter NREM stage 3 (6 ±4% vs 9 ±2%, p < 0.01) and NREM stage 4 (4 ±4% vs 13 ±2%, p < 0.01). No differences were observed in the total sleep night-time among the 3 groups. There was no correlation between EFV trough levels and the development of sleep abnormalities.

Conclusions: HIV⁺ pts on EFV complaining insomnia often show severe alterations in sleep architecture, as demonstrated in ambulatory EEG monitoring. In addition to overall lower sleep efficacy, characteristic reductions in REM and NREM stages 3 and 4 (deep sleep) in subjects on EFV, complaining or not insomnia, could be associated with cognitive dysfunction and fatigue, respectively.