The commonest side-effects of efavirenz occur in the brain. Trials have shown that 14 to 50% of people who take efavirenz develop side-effects in the first few months of treatment including drowsiness or insomnia, dizziness, vivid dreams and nightmares, confusion, abnormal thinking, impaired concentration, loss of memory, agitation, feeling ‘out-of-sorts’ or ‘stoned’, hallucinations, delusions, euphoria, and depression.1 Some of these side-effects are attributed to the detrimental impact efavirenz has on sleep.

The existence of the psychiatric side-effects of efavirenz, including depression, suicidal ideation, aggression, paranoia and mania is controversial. Some studies have found no links between these effects and efavirenz use.2 If they are real, however, it is certain that they are rare, although they may be more common in people with a history of psychiatric disorders.3 Only 1% of people in trials discontinued efavirenz due to psychiatric side-effects.

Side-effects are most likely to occur in the first two to four weeks of treatment, after which they tend to diminish markedly.4 However, there is some evidence that symptoms like mild anxiety and bad dreams may persist in up to half of people for over six months, or even while treatment continues.5 6 7 Despite their frequency, most people experience only mild to moderate symptoms and trials indicate that only 3% of people stop taking efavirenz because of side-effects.

The manufacturer currently recommends that efavirenz be taken before going to bed, since the feelings of dizziness and anxiety are likely to be most intense in the hours leading up to the peak in drug level, usually about four hours after dosing. However, up to half of people prefer to take efavirenz in the morning, to avoid bad dreams, disturbed sleep, and morning drowsiness attributed to the drug.8

Because of a genetic variation, some people will metabolise efavirenz slower than others. This variation is common among people with a black African heritage and it may increase the risk of side-effects.9 10 11 Genetic testing for this variation is not currently available. Therapeutic drug monitoring may be used to identify people who are exposed to high concentrations of efavirenz.

Rash is also common in people taking efavirenz, affecting around a quarter of people in trials. It can usually be controlled using antihistamines and tends to resolve within a month of starting efavirenz-based therapy.

Gynaecomastia (enlargement of the breasts) has been observed in a small number of people taking efavirenz.12 13 A hypersensitivity reaction to efavirenz has also been reported in two individuals. Symptoms included rash, fever, abdominal pain, diarrhoea, dry cough and jaundice.14


  1. Gallego L et al. Analyzing sleep abnormailities in HIV-infected patients treated with efavirenz. Clin Infect Dis 38: 430-432, 2004
  2. Journot V et al. Use of efavirenz is not associated with a higher risk of depressive disorders: a substudy of the randomized clinical trial ALIZE-ANRS 099. Clin Infect Dis 42: 1790-1799, 2006
  3. Boly L et al. Depressive symptoms predict increased incidence of neuropsychiatric side-effects in patients treated with efavirenz. J Acquir Immune Defic Syndr 42: 514-516, 2006
  4. Clifford DB et al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med 143: 714-721, 2005
  5. Hawkins T et al. Comparison of neuropsychiatric side effects in an observational cohort of efavirenz- and protease inhibitor-treated patients. HIV Clin Trials 6: 187-196, 2005
  6. Moyle G et al. Changes in sleep quality and brain wave patterns following initiation of an efavirenz-containing triple antiretroviral regimen. HIV Med 7: 243-247, 2006
  7. Fumaz CR et al. Long-term neuropsychiatric disorders on efavirenz-based approaches: quality of life, psychologic issues, and adherence. J Acquir Immune Defic Syndr 38: 560-565, 2005
  8. Skeie L et al. Can efavirenz be taken in the morning? Third International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, abstract WePe12.3C03, 2005
  9. Burger D et al. Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism. Br J Clin Pharmacol 61: 148-154, 2006
  10. Haas D et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult Clinical Trials Group study. AIDS 18: 2391-2400, 2004
  11. Rodriguez-Novoa S et al. Influence of 516T>G polymorphisms at the gene encoding the CYP450-2B6 isoenzyme on efavirenz plasma concentrations in HIV-infected subjects. Clin Infect Dis 40: 1358-1361, 2005
  12. Mira JA et al. Gynaecomastia in HIV-infected men on highly active antiretroviral therapy: association with efavirenz and didanosine treatment. Antivir Ther 9: 511-517, 2004
  13. Qazi NA et al. Gynaecomastia without lipodystrophy in HIV-1-seropositive patients on efavirenz: an alternative hypothesis. AIDS 16: 506-507, 2002
  14. Bossi P et al. Hypersensitivity syndrome associated with efavirenz therapy. Clin Infect Dis 30: 227-228, 2000
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.