Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor of HIV-1, and the nucleoside reverse transcriptase inhibitor lamivudine (3TC) are key components of first-line antiretroviral therapy according to current guidelines [1]. Both are popular because of once-daily dosing and the paucity of long-term side effects [1]. Little is known about acute intoxications with these drugs [2,3]. We describe the effects of a voluntary intoxication in the HIV-negative daughter of a patient. Case report. A 17 year-old, healthy woman (165 cm, 50 kg) with no medication or illicit drug abuse ingested 26 tablets of EFV 600 mg (15.6 g) and 26 tablets of 3TC 150 mg (3.9 g) with the intention of committing suicide. Two and a half hours later, she was brought to the emergency room because she felt agitated and had lower abdominal pain. On admission, her vital signs were normal. She was somnolent, but oriented and coherent. She described feeling ‘high’ and ‘alienated’ with ‘artificial visual impressions’, but negated any hallucinations. Her gait was clumsy with a tendency to fall; the remainder of the neurological examination and the general clinical status were normal. Five hours after drug ingestion, the woman started vomiting and continued for several hours. The following day she had abdominal cramps, diarrhea and a generalized macular rash with pruritus. The diarrhea and rash resolved within 3 days, the neuropsychological symptoms and the postprandial cramps within 5 days. Wild, bizarre dreams persisted for 5 days. Haematology and blood chemistry analyses performed on admission, as well as 16, 42 and 118 h after the intoxication were normal with the exception of a serum creatinine kinase of 173 U/l (normal range, < 167 U/l) on admission. The EFV drug plasma level was measured after 118 h and the result was 1.2 mg/l (therapeutic range, 1–5 mg/l). For comparison, we plotted this value against the pharmacokinetic curve predicted a priori for an average treatment-naive adult according to a published pharmacokinetic population meta-analysis [4] (Fig. 1). The profile is based on a two-compartment model with first-order absorption. We then altered the pharmacokinetic parameters according to their variability reported in the population (Bayesian adaptation) to sketch an a posteriori profile passing near the observation. This individualized profile of maximum likelihood assumed both a smaller distribution volume and larger drug clearance, giving a peak plasma concentration estimate of about 90 mg/l and a half-life of 18 h.Fig. 1: Modelling of efavirenz (EFV) pharmacokinetics after a single dose of 15.6 g. Based on the measured plasma drug concentration (dot) and a published a priori pharmacokinetic profile after a single dose of EFV (continuous line), we modelled a maximum likelihood a posteriori profile for our individual patient (dashed line).Discussion. As far as we know, this is only the second report on a voluntary EFV intoxication. Despite presumably high drug plasma levels, toxicity was only mild and self-limiting. The observed central nervous and cutaneous symptoms were most probably related to EFV, as they represent classical side-effects of this drug and hardly ever occur with 3TC. Up to 50% of patients treated with EFV experience mild neuropsychological symptoms including dizziness, somnolence, insomnia, vivid dreams, confusion, amnesia, depression or agitation [1,5–7]. Two publications have reported a correlation between the frequency of central nervous system toxicity and EFV plasma concentrations so far [7,8]. Symptoms usually subside spontaneously within 2–4 weeks, but may cause treatment discontinuation in 2 to 6% of patients [1,7,8]. Several case reports have documented severe exacerbations upon start of treatment presenting with a manic syndrome [2]; confusion and aggression [3]; depression [3,6] or psychosis [9,10]. Only one report, however, has correlated central nervous system symptoms with excessive EFV plasma levels of 59.4 mg/l [3]. Maculopapular rashes have occurred in up to 26% of patients treated with EFV and mostly clear spontaneously [1]. The progression to Stevens–Johnson syndrome [1] or photosensitive drug eruptions are exclusively rare [11]. EFV is subject to extensive metabolism, mainly by the cytochrome P-450 2B6 isoenzyme [5]. This shows considerable inter-individual variability [7,12]. Accordingly, intoxication with EFV can be the result of exaggerated ingestion (our case, [2]) and/or slowed metabolism [3]. Unfortunately, we only measured plasma drug concentration once in our patient, at 118 h after EFV ingestion. The result was below the average concentration expected in a drug-naive patient. This can be explained by a smaller distribution volume and a higher clearance in our patient. The distribution volume of EFV is indeed characterized by a marked variability among individuals [4], while an increased drug clearance could be explained by some degree of auto-induction occurring between administration and sampling. EFV clearance has earlier been shown to increase with both dose and frequency of administration [4]. Taken together, EFV intoxication leads to an exaggeration of the known adverse effects. All adverse effects spontaneously resolve within a few days after drug discontinuation [9,10].