Morning dosing for dolutegravir-related insomnia and sleep disorders

Dear Sirs, We read with interest the article by Hoffmann et al. 1, reporting unexpected rates of neurological adverse events associated with dolutegravir (DTG)‐based therapy, in particular in women, subjects aged over > 60 years and subjects taking abacavir. Since June 2014, having successfully managed our first case of DTG‐related insomnia (within the ARIA 2 trial) by simply bringing forward the drug dosing from evening to morning, our large Italian outpatients’ clinic has recommended morning dosing to patients starting DTG. The rate of insomnia has been very low since then, and no one has reported dizziness or confusion, unlike those who bring forward efavirenz 3. Other Italian centres implemented the same strategy, suggesting morning dosing to those who were experiencing insomnia after starting DTG. The response was assessed with a dichotomic question (presence or absence of insomnia or sleep disorders) rather than questionnaires as most of the data were retrospective. The significance of the association of the risk factors indicated by Hoffman et al. with the outcome of dosing anticipation and with the proportion of subjects discontinuing DTG was calculated with the two‐tailed Fisher's exact test. Out of 1502 HIV‐1‐infected patients taking DTG, 3.5% had insomnia and sleep disorders. The symptoms were prevalent in > 60‐year‐old subjects and women (P < 0.0001 for both risk factors), while the association with abacavir was not statistically significant (P = 0.3978). Overall, three out of four patients presenting sleep disorders resolved the problem by bringing forward drug dosing, while 15.3% discontinued DTG because of this side effect (0.5% of the whole population). Four of eight patients had additional adverse events motivating discontinuation (agitation in two patients, dyspepsia in one patient and renal colic, a decrease in libido and malaise in one patient). There were no statistically significant differences related to gender, age or concomitant abacavir among those who did not improve with the morning dose. However, those subjects who took abacavir tended to have a better outcome after dosing in the morning and to discontinue less frequently (see Table 1). Table 1. Patients who developed insomnia or sleep disorders after the introduction of dolutegravir and symptom response to bringing forward dosing, overall and split by risk factors.