Detailed information

Efavirenz is an anti-HIV drug that reduces the amount of virus in the body. Anti-HIV drugs such as efavirenz slow down damage to the immune system and prevent the occurrence of AIDS-defining illnesses.

Efavirenz belongs to a class of drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Non-nucleoside reverse transcriptase inhibitors stop the activity of HIV’s reverse transcriptase enzyme, which is needed to copy the genetic code of HIV into a form that can be inserted into human cells.

Efavirenz, formerly known by the codename DMP 266, was developed by Du Pont Pharma. It was approved for HIV treatment in the United States in 1998, and the European licence was granted in May 1999.

Efavirenz is marketed by Bristol-Myers Squibb under the trade name Sustiva in the United States, United Kingdom, Ireland, France, Germany, Italy, and Spain. The trade name Stocrin is used by Merck Sharp & Dohme, who market the drug in other European countries, Australia, Brazil, Latin America, South Africa and other regions. Numerous generic versions of efavirenz, either alone or co-formulated with other drugs, are available.

Efavirenz is also available in a triple-drug combination tablet containing 600mg efavirenz, 200mg emtricitabine (FTC), and 300mg tenofovir disoproxil fumarate. It was approved in the United States in July 2006 and in the European Union and Canada in late 2007 with the trade name of Atripla. Generic versions are available, while branded Atripla is due to be withdrawn from sale at the end of 2021 due to infrequent use. 


Efavirenz  is a powerful anti-HIV drug that must be taken in combination with other antiretroviral drugs. It has been proven to reduce HIV-1 viral load to below 400 copies/ml within six months in 60 to 80% of people who have not previously taken any HIV treatments. Efavirenz is not active against HIV-2.

Efavirenz was recommended as a component of first-line antiretroviral treatment from 2002 on the basis of studies showing superior outcomes for people treated with efavirenz-based combinations when compared to protease inhibitor-based treatment or treatment based on nevirapine. (Staszewski) (Tashima) (Arribas) (Schafer) (Robbins) (INITIO) (van Leth) (Riddler)

More recent studies have shown that the integrase inhibitor dolutegravir is more effective than efavirenz, and that the NNRTI rilpivirine is better tolerated (although less effective than efavirenz in people with high viral load, above 100,000 copies/ml).

Treatment guidelines now recommend the use of efavirenz as an alternative if newer drugs are unsuitable. But as newer drugs are better tolerated and have fewer drug interactions, efavirenz is rarely prescribed nowadays.

Taking it

Efavirenz  is dosed at 600mg, taken in the form of three 200mg capsules or one 600mg tablet once a day. The drug should be taken on an empty stomach before going to bed in order to reduce the risk of side effects. Taking the drug with food may increase drug levels in some people by up to 50%. High-fat meals may increase the absorption of efavirenz, which may in turn increase the risk of side effects, especially during the early weeks of treatment.



How well something works (in real life conditions). See also 'efficacy'.


A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

non-nucleoside reverse transcriptase inhibitor (NNRTI)

Non-nucleoside reverse transcriptase inhibitor, the family of antiretrovirals which includes efavirenz, nevirapine, etravirine, doravirine and rilpivirine. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to and block HIV reverse transcriptase (an HIV enzyme), preventing HIV from replicating.


A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.


Clear, non-cellular portion of the blood, containing antibodies and other proteins and chemicals.


See efavirenz/emtricitabine/tenofovir disoproxil fumarate for information on taking this combination pill.

It is important to take the drug as prescribed in order to maintain the right level of the drug in the blood. If blood levels of the drug fall too low, this will help the development of resistance to efavirenz and may affect future treatment options.

Efavirenz is also available as a solution for use in children and people who cannot take the tablets or capsules.

Side effects

The commonest side effects of efavirenz are rash, itching, abnormal dreams, difficulty concentrating, dizziness, headache, difficulty sleeping, drowsiness, abdominal pain, diarrhoea, nausea, vomiting, tiredness, anxiety, depression, raised triglyceride and liver enzyme levels.

Trials have shown that 14 to 50% of people who take efavirenz develop neurological 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. (Gallego) Some of these side effects are attributed to the detrimental impact efavirenz has on sleep.

Psychiatric side effects of efavirenz, including depression, suicidal ideation, aggression, paranoia and mania are rare, although they may be more common in people with a history of psychiatric disorders. (Journot) (Boly) Only 1% of people in trials discontinued efavirenz due to psychiatric side effects.

Neurological side effects are most likely to occur in the first two to four weeks of treatment, after which they tend to diminish markedly. (Clifford) 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. (Hawkins) (Moyle) (Fumaz) 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 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. (Skeie)

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. (Burger) (Haas) (Rodriguez-Novoa) 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. (Mira) (Qazi) A hypersensitivity reaction to efavirenz has also been reported in two individuals. Symptoms included rash, fever, abdominal pain, diarrhoea, dry cough and jaundice. (Bossi)


As with all other anti-HIV drugs, strains of HIV that are resistant to efavirenz may be transmitted or may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug. Even small amounts of transmitted efavirenz-resistant virus may also curtail the drug's effectiveness. If blood levels of the drug fall too low, this will help the development of resistance to efavirenz and may affect future treatment options.

Drug interactions

Although rarely used in combination with other antiretrovirals nowadays, efavirenz alters the levels of most protease inhibitors and usually requires adjusted dosing. Efavirenz is not administered with the other NNRTI drugs etravirine and nevirapine due to elevated side effect risk. (van Leth)

The following drugs should be avoided when taking efavirenz because the possibility of decreased metabolism when taken with efavirenz could possibly lead to life-threatening adverse events such as cardiac arrhythmias, prolonged sedation, or respiratory distress:  

  • Midazolam (Hyponovel, Versed)
  • Pimozide (Orap)

Other drugs to be avoided when on efavirenz  include:

  • Amodiaquine (Cameoing, Flavouring), due to risk of elevated liver enzymes
  • Clarithromycin (Claiosip, Klaricid, Klaricid XL, Bioxin) levels reduced and there have been reported high incidences of rash. Use of azithromycin can be considered
  • Gingko biloba can decrease efavirenz levels (Wiegman)
  • Hypericin (St John’s Wort) can reduce efavirenz levels
  • Milk thistle has a possibility of interaction.
  • Elbasvir and grazoprevir (Zepatier), or sofosbuvir/velpatasvir (Epclusa) or sofosbuvir/velpatasvir/voxilaprevir (Vosevi) or glecapravir/pibrentasvir (Maviret) for hepatitis C treatment, due to the risk of lowered blood levels of at least one direct-acting antiviral in each product.

The following drugs need to be administered at non-standard doses in people taking efavirenz:

  • Anticoagulants. Warfarin (Coumadin) levels may be increased or decreased. Monitor INR and adjust warfarin as needed.
  • Anticonvulsants. Phenytoin (Epanutin, Dilantin), phenobarbital (Luminol), and carbamazepine (Tegretol) may need to be given at lower doses to prevent reduction in efavirenz level. Anticonvulsant plasma levels should be monitored or possibly use therapeutic drug monitoring for efavirenz. (Robertson) Alternative anticonvulsants to be considered include valproic acid, lamotrigine, levetiracetam, or topiramate.  
  • Antidepressants. Sertraline (Zoloft) levels may be decreased when given with efavirenz.
  • Antifungals. Itraconazole (Sporanox) and ketoconazole (Nizoral) may have decreased plasma concentration. Voriconazole (Vfend) is usually not co-prescribed with efavirenz because of the risk of low voriconazole/elevated efavirenz levels. If drugs need to be used concomitantly, voriconazole dosing should be increased from 200 to 400mg and given every 12 hours; once-daily dosing of efavirenz should be decreased from 600 to 300mg.
  • Anti-infectives. Rifabutin (Mycobutin) levels are decreased by 35%, so consider dosing rifabutin once daily 450-600mg, or 3 times per week at 600mg, if efavirenz is not being given with a protease inhibitor.(Weiner) (Adult Prevention and Treatment of Opportunistic Infections Guidelines Working Group) As rifampicin decreases efavirenz levels by an average of 25%, individuals at the normal efavirenz dose of 600mg once daily should be monitored for response. In those weighing over 60kg, consider increasing the daily dose to 800mg. Results from the British CHIC study indicated that Black ethnicity was associated with higher efavirenz levels and increased weight contributed to lower efavirenz concentrations. (Stöhr) An earlier study in Thai patients, who were mainly under 55kg, found that the 600mg dose of efavirenz was effective. (Manosuthi)
  • Antimalarials. Artemether and mefloquine serum levels may be decreased, so monitoring is needed (i.e. mefloquine serum level, parasite count on blood smear, clinical signs of improvement).
  • Chemotherapy agents paclitaxel tamoxifen, vinblastine, and vincristine may have lessened serum concentrations; drug levels should be monitored.
  • Contraceptives. Ethinyl estradiol may have an interaction with efavirenz. Use of barrier contraception is recommended in addition to oral contraceptives to prevent pregnancy.
  • Immunosuppressants. Cyclosporine (Neoral, Sandimmune), sirolimus, tacrolimus, drugs mainly used after transplant surgery, should be dosed according to serum levels, as each may be decreased when taken with efavirenz. (Tseng)
  • Opioids. Methadone hydrochloride (Methadose) may need to be given at a higher dose in people taking efavirenz. (Clarke) The dose should be increased in 10mg steps if withdrawal symptoms appear.
  • Statins. Atorvastatin (Lipitor), pravastatin (Pravachol), and simvastatin (Zocor) may need to be given at a higher dose to achieve target lipid goals, but require monitoring to avoid possible toxicity. (Gerber)

Efavirenz may cause a false-positive result if the CEDIA DAU Multi-Level THC assay is used. Other types of tests do not confuse efavirenz and cannabis.


Efavirenz is approved in the European Union and the United States for use in children with HIV infection aged three years and over. For children who weigh less than 40kg, the dose is adjusted for weight. A syrup formulation is available for children who find capsules difficult to take. Efavirenz has not been evaluated in children under three years of age or below 10kg in weight.


Efavirenz can be used during pregnancy, although experts in different countries and regions have arrived at different conclusions about when it is preferable to use it. Efavirenz is recommended as an alternative first-line drug in World Health Organization guidelines. National guidelines in the United Kingdom recommend newer drugs but do not advise against the use of efavirenz during pregnancy.

Previous treatment guidelines warned against the use of efavirenz during pregnancy based on findings from animal studies and a small number of case reports of neural tube defects in infants exposed to efavirenz during the first three months of gestation. (Fundaro)

It is now clear that birth defects do not occur at a higher rate in infants exposed to efavirenz.

A systematic review and meta-analysis of 23 studies, published in 2014, found that treatment with efavirenz during the first three months of pregnancy did not increase the risk of birth abnormalities. Amongst children born to women who received efavirenz in the first trimester, the overall incidence of birth abnormalities was 1.6%, and the prevalence of neural tube defects was 0.05%. Both figures are very close to the ranges reported in the general population in many developed and developing countries. (Ford) Similarly, an analysis of 24,963 births in 21,093 women with HIV showed that efavirenz use in the first trimester was not associated with an increased risk of birth abnormalities. (Martinez de Tejada)


Staszewski S et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. New England Journal of Medicine, 341: 1865-1873, 1999.

Tashima K et al. Durable viral suppression on EFV-based HAART: 168 weeks of follow-up. 15th International AIDS Conference, Bangkok, abstract TuPeB4547, 2004.

Arribas JR et al. High effectiveness of efavirenz-based highly active antiretroviral therapy in HIV-1-infected patients with fewer than 100 CD4 cells/ul and opportunistic diseases: the EfaVIP study (efavirenz in very immunosuppressed patients). AIDS, 16: 1554-1556, 2002.

Schafer R et al. Antiretroviral strategies in naive HIV+ subjects: comparison of 4-drug versus sequential 3-drug regimens (ACTG 384). 14th International AIDS Conference, Barcelona, abstract LbOr20B, 2002.

Robbins G et al. Antiretroviral strategies in naive HIV+ subjects: comparisons of sequential 3-drug regimens (ACTG 384). 14th International Conference on AIDS, Barcelona, abstract LbOr20A, 2002.

INITIO Trial Coordinating Committee et al. Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitors, protease inhibitor, or both in INITIO: open-label randomised trial. The Lancet, 368: 287-298, 2006.

van Leth F et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. The Lancet, 363: 1253-1263, 2004. You can read more about this study in our news report.

Riddler SA et al. Class-sparing regimens for initial treatment of HIV-1 infection. New England Journal of Medicine, 358: 2095-2106, 2008.

Gallego L et al. Analyzing sleep abnormailities in HIV-infected patients treated with efavirenz. Clinical Infectious Diseases, 38: 430-432, 2004. You can read more about this study in our news report.

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. Clinical Infectious Diseases, 42: 1790-1799, 2006. You can read more about this study in our news report.

Boly L et al. Depressive symptoms predict increased incidence of neuropsychiatric side-effects in patients treated with efavirenz. Journal of Acquired Immune Deficiency Syndromes, 42: 514-516, 2006. You can read more about this study in our news report.

Clifford DB et al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Annals of Internal Medicine, 143: 714-721, 2005. You can read more about this study in our news report.

Hawkins T et al. Comparison of neuropsychiatric side effects in an observational cohort of efavirenz- and protease inhibitor-treated patients. HIV Clinical Trials, 6: 187-196, 2005.

Moyle G et al. Changes in sleep quality and brain wave patterns following initiation of an efavirenz-containing triple antiretroviral regimen. HIV Medicine, 7: 243-247, 2006. You can read more about this study in our news report.

Fumaz CR et al. Long-term neuropsychiatric disorders on efavirenz-based approaches: quality of life, psychologic issues, and adherence. Journal of Acquired Immune Deficiency Syndromes, 38: 560-565, 2005. You can read more about this study in our news report.

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.

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. British Journal of Clinical Pharmacology, 61: 148-154, 2006.

Haas D et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult Clinical Trials Group study. AIDS, 18: 2391-2400, 2004.

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. Clinical Infectious Diseases, 40: 1358-1361, 2005.

Mira JA et al. Gynaecomastia in HIV-infected men on highly active antiretroviral therapy: association with efavirenz and didanosine treatment. Antiviral Therapy, 9: 511-517, 2004.

Qazi NA et al. Gynaecomastia without lipodystrophy in HIV-1-seropositive patients on efavirenz: an alternative hypothesis. AIDS, 16: 506-507, 2002.

Bossi P et al. Hypersensitivity syndrome associated with efavirenz therapy. Clinical Infectious Diseases, 30: 227-228, 2000.

Wiegman D-J et al. Interaction of Gingko biloba with efavirenz. AIDS, 23: 1184-85, 2009.

Robertson SM et al. A potentially significant interaction between efavirenz and phenytoin: a case report and review of the literature. Clinical Infectious Diseases, 41: e15-e18, 2005.

Weiner M et al. Evaluation of the drug interaction between rifabutin and efavirenz in patients with HIV infection and tuberculosis. Clinical Infectious Diseases, 41: 1343-1349, 2005. You can read more about this study in our news report.

Adult Prevention and Treatment of Opportunistic Infections Guidelines Working Group. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents [June 18 2008 DRAFT version]. Available at: http://aidsinfo.nih.gov/contentfiles/Adult_OI.pdf. Accessed (30 November 2008), 2008.

Stöhr W et al. for the UK CHIC Study Factors influencing efavirenz and nevirapine plasma concentration: effect of ethnicity, weight and co-medication. Antiviral Therapy, 13: 675-685, 2008.

Manosuthi W et al. Efavirenz 600 mg/day versus efavirenz 800 mg/day in HIV-infected patients with tuberculosis receiving rifampicin: 48 weeks results. AIDS, 20: 131-132, 2006.

Tseng A et al. Probable interaction between efavirenz and cyclosporin. AIDS, 16: 505-506, 2002.

Clarke S et al. Managing methadone and non-nucleoside reverse transcriptase inhibitors: guidelines for clinical practice. Seventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 88, 2000.

Gerber JG et al. Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin and pravastatin. Results of AIDS Clinical Trials Group 5108 Study. Journal of Acquired Immune Deficiency Syndromes, 39: 307-312, 2005.

Fundaro C et al. Myelomeningocele in a child with intrauterine exposure to efavirenz. AIDS, 16: 299-300, 2002.

Ford N et al. Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis. AIDS, 28: S123-131, 2014.

Martinez de Tejada B et al. Birth defects following exposure to efavirenz-based antiretroviral therapy at conception/first trimester of pregnancy: a multi-cohort analysis. Journal of Acquired Immune Deficiency Syndromes, 80: 316-324. 2019. You can read more about this study in our news report.

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