Sustiva

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 functions by binding directly to reverse transcriptase, blocking RNA-dependent and DNA-dependent DNA polymerase activities. This mechanism effectively suppresses viral replication, reduces plasma HIV-RNA levels, and increases CD4 cell counts. Clinical studies have demonstrated its potent antiviral efficacy, convenient once-daily dosing, and established role in both treatment-naïve and experienced patients, subject to resistance testing. Proper adherence is critical to maintaining viral suppression and minimizing the development of resistance.

Features

• Active ingredient: Efavirenz 600 mg
• Pharmacologic class: Non-nucleoside reverse transcriptase inhibitor (NNRTI)
• Standard dosage form: Film-coated tablets
• Administration: Oral, once daily
• Half-life: 40–55 hours (after single dose), 52–76 hours (after multiple doses)
• Metabolism: Primarily hepatic via CYP3A4 and CYP2B6
• Excretion: Primarily fecal (14–34% as metabolites), renal (<1% unchanged)

Benefits

• Provides potent and sustained suppression of HIV-1 viral load
• Supports immune reconstitution through increased CD4+ T-cell counts
• Enables simplified once-daily dosing, supporting long-term adherence
• Demonstrates high genetic barrier to resistance within its class
• Suitable for use in combination with a broad range of other antiretroviral agents
• Supported by extensive long-term clinical efficacy and safety data

Common use

Sustiva is used as part of a combination antiretroviral therapy regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 40 kg. It is commonly prescribed for 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. Use should be guided by HIV genotypic resistance testing where available to ensure susceptibility. It is not recommended as monotherapy due to the high risk of rapid resistance development.

Dosage and direction

The recommended adult dosage is 600 mg orally once daily. It should be taken on an empty stomach, preferably at bedtime, to improve tolerability of nervous system symptoms during the initial treatment period. For patients unable to tolerate the 600 mg dose, a temporary dose reduction to 400 mg once daily may be considered under close supervision, though this is not the standard recommended dosing. Pediatric dosing is based on body weight and must be calculated precisely according to prescribing guidelines. Tablets should be swallowed whole with water; they should not be crushed, chewed, or broken. Dosage adjustment is recommended in patients with hepatic impairment.

Precautions

Sustiva has been associated with serious psychiatric symptoms including severe depression, suicidal ideation, and aggressive behavior. Patients with a history of psychiatric illness should be monitored closely. It may cause dizziness, impaired concentration, and somnolence, particularly during the first weeks of therapy; patients should avoid driving or operating machinery if affected. Hepatic transaminases should be monitored before and during treatment. Use with caution in patients with hepatitis B or C co-infection due to increased risk of hepatic toxicity. Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues used in combination. Fat redistribution and metabolic abnormalities may occur. Pregnancy should be avoided due to risk of fetal harm; women of childbearing potential must use effective contraception.

Contraindications

Sustiva is contraindicated in patients with known hypersensitivity to efavirenz or any component of the formulation. Coadministration with elbasvir/grazoprevir, voriconazole, cisapride, midazolam, pimozide, triazolam, or ergot derivatives is contraindicated due to potential for serious and/or life-threatening reactions. It should not be administered concurrently with other NNRTIs unless specifically indicated. Use is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).

Possible side effect

Common side effects (≥10%) include: rash, dizziness, headache, fatigue, insomnia, abnormal dreams, nausea, and diarrhea. Serious side effects may include: severe skin reactions (Stevens-Johnson syndrome, erythema multiforme), psychiatric symptoms (depression, suicidal ideation, psychosis), hepatotoxicity, seizures, and immune reconstitution syndrome. Less common but clinically significant effects include: hyperlipidemia, increased amylase, gynecomastia, and QT prolongation. Most nervous system symptoms improve within 2–4 weeks of continued therapy.

Drug interaction

Sustiva is a moderate inducer of CYP3A4 and may decrease concentrations of drugs metabolized by this pathway. It should not be coadministered with St. John’s wort. Significant interactions occur with: anticonvulsants (carbamazepine, phenobarbital), antifungals (voriconazole contraindicated), antimycobacterials (rifampin, rifabutin), certain antidepressants, sedatives, and statins. It may reduce the effectiveness of hormonal contraceptives; alternative non-hormonal methods are recommended. Coadministration with other CYP3A4 inducers or inhibitors requires careful monitoring and potential dosage adjustments.

Missed dose

If a dose is missed, it should be taken as soon as possible unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Doubling doses is not recommended. Consistent adherence is critical to maintain viral suppression and prevent resistance development. Patients should be counseled on the importance of strict adherence and strategies to avoid missed doses.

Overdose

There is limited experience with Sustiva overdose. Symptoms may include increased nervous system symptoms, involuntary muscle contractions, and elevated liver enzymes. There is no specific antidote; treatment should consist of general supportive measures including monitoring of vital signs and ECG. Since efavirenz is highly protein-bound, dialysis is unlikely to be beneficial. Gastric lavage may be considered if administered shortly after ingestion. Medical toxicology consultation is recommended.

Storage

Store at 25°C (77°F); excursions permitted between 15°–30°C (59°–86°F). Keep in the original container with the lid tightly closed to protect from moisture. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging. Do not store in bathroom or other areas with high humidity.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Treatment decisions must be made by a qualified healthcare professional based on individual patient characteristics. Always consult the full prescribing information and clinical guidelines before initiating therapy. Dosage and administration may vary based on patient factors including renal/hepatic function, drug interactions, and treatment history. Not all side effects or interactions are listed here.

Reviews

Clinical trials and post-marketing experience have established Sustiva as a effective component of antiretroviral therapy. In study 006, 70% of treatment-naïve patients achieved viral load <400 copies/mL at 48 weeks when combined with zidovudine/lamivudine. Many clinicians report good long-term virologic control with once-daily dosing, though some patients discontinue due to CNS effects. Real-world evidence supports its durability in maintained regimens, though resistance patterns have evolved over time. Patient experiences vary regarding tolerability, with many adapting to initial side effects while others require regimen modification.