1- left untreated.The HIV virus is carried by

1- Background:Efavirenz is classified as a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is recommended as the treatment of choice to treat patients with the human immunodeficiency virus (HIV-1) infection. Efavirenz is usually used in a regimen with two other reverse transcriptase inhibitors, such as Tenofovir and Emtricitabine. Efavirenz triple combination has a good antiretroviral efficacy which is confirmed in a number of clinical trials.2- HIV: HIV is classified as a lentivirus, which is a subgroup of retrovirus. The immunodeficiency syndrome (AIDS) is caused as a consequence of this viral infection which leads to the failure of the human immune system allowing cancers and opportunistic infections to survive and grow inside the body. Depending on the subtype of the virus, patients can live approximately 9-11 years after being infected with the HIV virus if they left untreated.The HIV virus is carried by blood, semen, pre-ejaculate, and vaginal fluids, and the infection can happen by the transfer of any of these fluids. The two types of HIV virus are HIV-1 and HIV-2. These subtypes are distinct viruses and are genetically different from each other. In addition, these two subtypes can be specifically detected by clinical tests due to the presence of genetic variations between them.The predominant subtype is HIV-1 and accounts for approximately 95% of AIDS cases around the world.3- Chemical structure:The IUPAC name of Efavirenz is (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one, with an empirical formula of C14H9ClF3NO2 and a molecular weight of 315.68 g/mol-1. Efavirenz is considered practically insoluble in water with a water solubility of less than 10 µg/ml. Figure 1 presents the chemical structure of Efavirenz.Figure 1: The molecular structure of Efavirenz. 4- Mode of action and Molecular target:Efavirenz is classified as a non-nucleoside reverse transcriptase inhibitor (NNRTI), a subgroup of antiretrovirals. The reverse transcriptase enzyme is vital for the transcription of viral RNA into DNA, thus, inhibiting this enzyme stops the replication of the virus. NNRTIs bind to a distinct binding pocket of the enzyme called the NNRTI pocket, while the nucleoside reverse transcriptase inhibitors bind within the active site of the enzyme. Efavirenz is only effective against HIV-1 as the binding pocket of the HIV-2 reverse transcriptase is structurally different from that of HIV-1. 5- Pharmacokinetics:The bioavailability of Efavirenz after oral administration is good, therefore, it is available in different oral dosage forms such as capsules (50, 100 or 200 mg), film-coated tablets (600 mg), and liquid dosage forms containing 30 mg/ml. Efavirenzreaches its peak plasma concentration after around 3 to 5 hours of administration and reaches its steady state in the range of 6 to 10 days. The peak plasma concentration and the area under the curve of Efavirenz are highly affected by the presence of food. The Cmax and AUC will be increased after the ingestion of food compared with administering the drug while fasting. Efavirenzis lipophilic in nature, thus crossing the blood brain barrier easily. Its concentration in the cerebrospinal fluid can reach 0.26 – 1.19% of the blood plasma concentration 26. Efavirenz has a high binding affinity to plasma proteins of around 99.5 to 99.75%, especially to Albumin. In addition, Efavirenz undergoes metabolism by the liver CYP450 enzymes, mainly CYP2B6 and CYP3A4, through hydroxylation, and then subsequently glucuronidation to give the metabolisedcompounds 28).The half-life of Efavirenz is ranging from 52 to 76 hours and it is predominantly excreted in the feces. Patients with kidney problems such as renal insufficiency do not need dose adjustment as less than 1% of Efavirenz is eliminated in the urine 29. 6- Clinical activity:The clinical trials have shown that regimens containing Efavirenz showed better antiretroviral efficacy than the triple regimens which do not contain Efavirenz and almost similar to regimens containing protease inhibitors. However, there is no study has similar results as that of the Abbott 720 study 102.  7- Pathophysiology:Efavirenz is considered to be safe. The most common adverse reactions are including neurologic events such as dizziness, somnolence, depression, aggressive behavior, and manic reactions. Those neurologic side effects are usually temporary and rarely leading to the discontinuation of Efavirenz treatment. Other frequent side effects occurring with the use of Efavirenzare rash and hepatitis which can be diminished with continuous treatment, while these side effects can be life-threatening as a consequence of using Nevirapine containing regimens. One major advantage of prescribing Efavirenz is the low probability of developing Dyslipidaemia after using Efavirenz compared tousing regimens containing protease inhibitors, especially Ritonavir. 8- Conclusion:Efavirenz is considered as one of the keystones in the contemporary fight against the HIV infections and can be a benchmark for developing novel antiretrovirals. The dose recommendation for Efavirenz is to be administered once daily in tablets form. Caution to be taken when co-administering Efavirenz with other drugs that are metabolized by the CYP450 enzymes as it induces the activity of these enzymes leading to a lower bioavailability of the co-administered drugs. Efavirenz-based regimens are widely prescribed for patients with HIV-1 infections not only because of its better clinical efficacy, but also due to its less severe adverse reactions and longer half-life compared with other antiretroviral agents.