Efavirenz is an FDA-approved medication used for the treatment and prevention of HIV. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Like the majority of other NNRTI agents, its most common use is in combination with other agents with different mechanisms of action in antiretroviral therapy (ART) regimens. Due to its unfavorable side effect profile, it has fallen somewhat out of favor.[1]

• FDA-labeled indications
  • HIV infection
• Non-FDA labeled indications
  • HIV infection prophylaxis (occupational exposure, perinatal transmission)

Efavirenz is a non-nucleoside reverse transcriptase inhibitor drug (NNRTI). It binds to a non-catalytic site of the HIV reverse transcription enzyme, thereby inhibiting its activity. This action consequently blocks DNA polymerase activities, including HIV replication. Though therapeutic drug concentration monitoring is not necessary for efavirenz, it is essential to achieve adequate serum concentrations. Low concentrations are associated with virologic failure, while higher concentrations are associated with increased adverse effects such as sleep disorders.[2]

The administration of efavirenz with food has shown to increase the serum concentrations and the incidence of side effects. For this reason, patients should not take efavirenz with food.[3] Peak concentrations are reached by 5 hours following a single oral dose, with steady-state plasma concentrations achieved in 6 to 7 days. The half-life of efavirenz is roughly 45 hours, making once-daily dosing suitable. Efavirenz is highly protein bound to human plasma proteins, predominantly albumin. Efavirenz converts to inactive hydroxylated metabolites by the action of the CYP3A4 enzyme.[4] 

It is available in combination with other antiviral medications.[5]

Efavirenz is available by prescription only, and it is available as an oral capsule and an oral tablet. It is also available as a component of two combination drugs: efavirenz, emtricitabine, and tenofovir disoproxil fumarate, and efavirenz, lamivudine, and tenofovir disoproxil fumarate. The capsules are available as 200 mg and 50 mg, while the tablets are available as 600 mg. The recommended adult dose is 600 mg per day, but there has been data showing that 400 mg per day yields equivalent outcomes with fewer side effects.[6]

The manufacturer recommends no renal dose adjustments. No dose adjustments are necessary for mild hepatic impairment (Child-Pugh class A), but caution is advisable. Efavirenz is not recommended in patients with moderate to severe impairment (Child-Pugh class B or C).

Efavirenz dosing should be on an empty stomach, as increased efavirenz serum concentrations occur when taken with food. Increased serum concentrations can lead to increased adverse effects.[7] 

NNRTIs as a drug class are commonly associated with central nervous system (CNS) effects. Among these are impaired concentration, vivid or abnormal dreams, insomnia, suicidal ideation, nausea, and vomiting.[8] Patients who experience these adverse effects are more likely to be non-adherent and discontinue their antiretroviral therapy, leading to virologic failure.[9] These symptoms typically arise in the first few days of treatment and decline within a few weeks of continued therapy.[4]

Like the majority of the NNRTIs, efavirenz correlates with a wide array of drug interactions due to the phase I cytochrome P450 (CYP) enzymes. Efavirenz is a substrate, inducer, and inhibitor of CYP3A4.[10] 

Lipodystrophy is also a class-wide effect of NNRTIs and may occur during treatment with efavirenz.[4]

The use of efavirenz is contraindicated in patients with previously documented hypersensitivity to efavirenz and patients concurrently receiving elbasvir/grazoprevir due to a CYP3A4 interaction. Efavirenz acts as a CYP3A4 inducer, in this case, by decreasing the serum concentrations of grazoprevir.[11] The use of efavirenz is also contraindicated in pregnant women in the first trimester due to reports of neural tube defects.