Sustiva (efavirenz) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. As a cornerstone of many highly active antiretroviral therapy (HAART) regimens, it works by binding directly to reverse transcriptase, blocking RNA-dependent and DNA-dependent DNA polymerase activities. Its high barrier to resistance and once-daily dosing support long-term viral suppression and adherence, making it a preferred option in both treatment-naïve and experienced patients under clinical guidance.

Features

• Active ingredient: Efavirenz 600 mg
• Pharmacologic class: Non-nucleoside reverse transcriptase inhibitor (NNRTI)
• Standard formulation: Film-coated tablets
• Dosing frequency: Once daily
• Half-life: 40–55 hours
• Metabolism: Primarily hepatic via CYP3A4 and CYP2B6
• Excretion: Feces (14–34%) and urine (<1% as unchanged drug)

Benefits

• Provides potent and sustained suppression of HIV-1 viral load
• Supports adherence through simple once-daily oral dosing
• Demonstrates a high genetic barrier to resistance development
• Suitable for use in combination with a wide range of other antiretroviral agents
• Well-established long-term efficacy and safety profile in diverse patient populations
• Available in fixed-dose combinations for simplified regimen management

Common use

Sustiva is used as part of combination antiretroviral therapy for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 40 kg. It is commonly prescribed in treatment-naïve individuals and may be used in certain treatment-experienced patients with no evidence of viral resistance to efavirenz. It is often combined with nucleoside reverse transcriptase inhibitors such as tenofovir and emtricitabine. Clinical use is guided by resistance testing, treatment history, and patient-specific factors including comorbidities and concomitant medications.

Dosage and direction

The recommended adult dosage is 600 mg orally once daily. Take on an empty stomach, preferably at bedtime, to improve tolerability of nervous system symptoms during the initial treatment period. For patients unable to swallow tablets, the tablet may be dissolved in a small amount of water. Dosage adjustment is required when coadministered with strong CYP3A inducers or inhibitors. In pediatric patients, dosing is based on body weight and must be calculated precisely. Do not crush, break, or chew tablets.

Precautions

• Severe psychiatric symptoms: Monitor for depression, suicidal ideation, and severe psychiatric events
• Nervous system symptoms: Dizziness, insomnia, impaired concentration, and drowsiness are common, particularly during the first weeks of therapy
• Hepatotoxicity: Monitor liver function before and during treatment; discontinue if severe hepatic impairment occurs
• Lipid effects: May increase total cholesterol and triglycerides; monitor lipid profile periodically
• Pregnancy: Not recommended during the first trimester due to risk of neural tube defects; use effective contraception
• Rash: Usually mild to moderate and self-limiting; discontinue if severe rash or rash with systemic symptoms occurs

Contraindications

• Hypersensitivity to efavirenz or any component of the formulation
• Coadministration with elbasvir/grazoprevir, voriconazole, or other drugs highly dependent on CYP3A4 for clearance with narrow therapeutic indices
• Concomitant use with St. John’s wort due to reduced efavirenz concentrations
• Severe hepatic impairment (Child-Pugh Class C)
• History of serious psychiatric events attributed to prior efavirenz use

Possible side effects

Common (≥10%):

• Dizziness
• Insomnia
• Fatigue
• Abnormal dreams
• Rash
• Nausea
• Headache

Less common (1–10%):

• Depression
• Anxiety
• Impaired concentration
• Increased liver enzymes
• Diarrhea
• Vomiting

Rare (<1%):

• Severe skin reactions (Stevens-Johnson syndrome)
• Hepatotoxicity with hepatic failure
• Suicidal ideation
• Gynecomastia
• Convulsions

Drug interaction

Sustiva is a moderate inducer of CYP3A4 and may alter concentrations of many drugs. Significant interactions include:

• Reduced concentrations: Atazanavir, boceprevir, clarithromycin, itraconazole, ketoconazole, posaconazole, rifabutin, voriconazole, warfarin, and hormonal contraceptives
• Increased concentrations: Rilpivirine, saquinavir
• Variable effects: Methadone (may require dosage adjustment)
• Contraindicated combinations: Elbasvir/grazoprevir, voriconazole
• Monitor closely: Anticonvulsants, antidepressants, immunosuppressants, and statins

Missed dose

If a dose is missed, take it as soon as possible unless it is almost time for the next dose. Do not double the next dose. Maintaining consistent dosing is critical to avoid subtherapeutic concentrations and potential development of resistance. If vomiting occurs within hours of dosing, do not redose; wait until the next scheduled dose.

Overdose

Experience with efavirenz overdose is limited. Symptoms may include increased nervous system symptoms, involuntary muscle contractions, and elevated liver enzymes. There is no specific antidote. Management includes supportive care and monitoring of vital signs. Hemodialysis is unlikely to be effective due to high protein binding. Contact a poison control center for latest guidance.

Storage

Store at 25°C (77°F); excursions permitted between 15–30°C (59–86°F). Keep in original container with tightly closed lid to protect from moisture. Keep out of reach of children and pets. Do not use if tablets are discolored or show signs of deterioration.

Disclaimer

This information is for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting or changing any medication regimen. Individual patient needs and circumstances may vary. Full prescribing information should be reviewed before administration.

Reviews

Sustiva has been extensively studied in clinical trials and real-world settings over two decades. The ACTG 5095 study demonstrated superior virologic suppression compared to other regimens in treatment-naïve patients. Long-term follow-up in the STARTMRK trial confirmed durable efficacy with consistent safety profile. Many clinicians appreciate its once-daily dosing and high barrier to resistance, though note the need for careful patient selection and monitoring for neuropsychiatric effects. Patient-reported outcomes indicate high satisfaction with regimen simplicity, though some report persistent CNS effects affecting quality of life.