Efavirenz is a non‑nucleoside reverse transcriptase inhibitor (NNRTI) marketed under the brand name Sustiva, used in first‑line antiretroviral therapy (ART) for HIV‑1 infection. It works by binding directly to the reverse transcriptase enzyme, halting viral RNA synthesis. Since its launch in 1998, efavirenz has become a benchmark for NNRTI‑based regimens, but newer agents claim better tolerability and higher resistance barriers. This guide breaks down the key facts, compares efavirenz with the most common alternatives, and gives a quick checklist for clinicians, pharmacists, and patients.
Current WHO guidelines still list efavirenz‑based triple therapy (efavirenz+two nucleoside reverse transcriptase inhibitors) as an acceptable first‑line option, especially where cost is a major factor. The drug’s long half‑life (~48hours) supports once‑daily dosing, which helps adherence. However, its metabolic pathway via CYP2B6 means it interacts with many anticonvulsants and antibiotics, demanding careful review of comorbid meds.
| Drug | Class | Typical Dose | Resistance Barrier | Common Side Effects | Pregnancy Category |
|---|---|---|---|---|---|
| Efavirenz | NNRTI | 600mg once daily | Low‑moderate | Central nervous system (dizziness, vivid dreams), rash | Category D (risk of neural‑tube defects) |
| Nevirapine | NNRTI | 200mg→400mg once daily | Low | Hepatotoxicity, rash | Category B |
| Rilpivirine | NNRTI | 25mg once daily (fasted) | Moderate | Rash, insomnia | Category C |
| Dolutegravir | INSTI | 50mg once daily | High | Insomnia, headache, mild weight gain | Category B (preferred for pregnancy) |
| Bictegravir | INSTI | 50mg once daily (fixed‑dose combo) | High | Low incidence of GI upset | Category B |
Despite newer drugs, efavirenz remains a solid choice in several scenarios:
Switching or starting with another agent makes sense when any of the following apply:
Efavirenz’s hallmark is its central nervous system (CNS) toxicity. Studies from 2019‑2022 show that up to 30% of patients report vivid dreams or dizziness during the first two weeks, with a gradual decline over time. In contrast, rilpivirine’s CNS impact is minimal, while dolutegravir’s most common complaints are mild insomnia and headache.
Rash with efavirenz occurs in about 5% of users, occasionally progressing to Stevens‑Johnson syndrome-though rare. Nevirapine carries a higher hepatotoxicity risk, especially in women with higher CD4 counts.
Because efavirenz is metabolized primarily by CYP2B6, any drug that induces or inhibits this enzyme can shift efavirenz plasma levels by 30‑50%.
When such agents are unavoidable, therapeutic drug monitoring (TDM) can guide dose adjustments, or clinicians may opt for an INSTI that bypasses CYP pathways.
Generic efavirenz is widely available through national procurement programs, often at less than $0.10 per tablet. Dolutegravir and bictegravir, while now off‑patent in many regions, still carry higher list prices, though they are frequently covered by tier‑2 insurance plans with co‑pay assistance.
For patients in low‑ and middle‑income countries, the WHO’s “Rapid Transition” initiative encourages a gradual shift to INSTI‑based regimens where funding permits, but efavirenz remains a fallback due to its low cost and extensive safety data.
Use the following mental model when choosing between efavirenz and alternatives:
Understanding efavirenz in context opens doors to deeper topics:
If you need a tried‑and‑true, low‑cost NNRTI and your patient tolerates it well, efavirenz remains a viable option. However, for those concerned about CNS side effects, pregnancy safety, or resistance, newer INSTIs like dolutegravir or bictegravir often provide a smoother experience, albeit at a higher price point.
Light to moderate alcohol usually doesn’t affect efavirenz levels, but binge drinking can increase CNS side effects like dizziness and vivid dreams. It’s safest to limit alcohol while the body adjusts to the medication.
Efavirenz crosses the blood‑brain barrier and binds to CNS receptors, which can alter sleep architecture. Most patients notice the effect during the first two weeks, and it typically wanes after a month.
Efavirenz is classified as Category D because early‑pregnancy exposure has been linked to neural‑tube defects in animal studies. Current WHO guidance recommends using an INSTI‑based regimen (dolutegravir or bictegravir) for women of child‑bearing potential.
Rifampin, a core TB drug, induces CYP2B6 and can cut efavirenz levels by up to 40%. Clinicians may increase efavirenz to 800mg daily, use therapeutic drug monitoring, or switch to an INSTI that isn’t affected by rifampin.
Baseline liver function tests and a CD4 count are recommended. Follow‑up labs at 4-8weeks check for hepatotoxicity and viral load. If neuropsychiatric symptoms persist beyond two weeks, consider a regimen change.
Yes. Bioequivalence studies performed by the FDA and EMA show that approved generic formulations have efavirenz exposure within 90‑110% of the brand product, offering the same viral suppression rates.
A direct switch is acceptable if the patient’s viral load is <50copies/mL and there are no resistance mutations to integrase inhibitors. Most guidelines advise a 24‑hour overlap to maintain drug levels, but many clinicians do a same‑day change.
Natalie Kelly
Great overview! If you’re just starting a regimen, remember to check for any over‑the‑counter meds that might mess with efavirenz levels.