What is the preferred treatment between efavirenz and dolutegravir for HIV-1 (Human Immunodeficiency Virus type 1) infection?

Dolutegravir is Preferred Over Efavirenz for HIV-1 Treatment

Dolutegravir-based regimens should be used as first-line therapy instead of efavirenz for HIV-1 infection, based on superior efficacy, better tolerability, higher barrier to resistance, and faster viral suppression. 1

Evidence Supporting Dolutegravir Superiority

Efficacy Outcomes

• Dolutegravir plus abacavir/lamivudine achieved 88% viral suppression (<50 copies/mL) at 48 weeks compared to 81% with efavirenz/TDF/emtricitabine (P=0.003), meeting superiority criteria. 2
• Viral suppression occurred significantly faster with dolutegravir (median 28 days) versus efavirenz (84 days, P<0.001). 2
• CD4+ T-cell count increases were greater with dolutegravir (267 cells/mm³) compared to efavirenz (208 cells/mm³, P<0.001). 2
• At 96 weeks, dolutegravir maintained 74% viral suppression versus 72% with low-dose efavirenz (400 mg), with significantly faster time to suppression (P<0.001). 3

Resistance Profile

• No participants receiving dolutegravir developed integrase or NRTI resistance mutations at virologic failure, demonstrating a high genetic barrier to resistance. 4, 2
• In contrast, efavirenz-treated patients developed 17 resistance mutations (efavirenz-associated with or without lamivudine/tenofovir mutations) among 19 patients with virologic failure. 3
• Dolutegravir remains effective against first-generation integrase inhibitor resistance. 5

Tolerability and Safety

• Discontinuation due to adverse events was significantly lower with dolutegravir (2%) versus efavirenz (10%). 2
• Efavirenz causes significantly higher rates of rash and central nervous system adverse effects (including abnormal dreams, anxiety, dizziness, somnolence) compared to integrase inhibitor-based therapy. 1
• Efavirenz carries increased risk of suicidality and should be avoided in patients with depression history. 1
• Insomnia was reported more frequently with dolutegravir, though overall tolerability remained superior. 2

Current Guideline Recommendations

First-Line Regimens (2024-2025)

The most recent guidelines recommend the following as preferred initial therapy 1:

• Bictegravir/TAF/FTC (evidence rating: AIa)
• Dolutegravir plus tenofovir/emtricitabine (evidence rating: AIa)
• Dolutegravir/lamivudine (only if HIV RNA <500,000 copies/mL, no lamivudine resistance, no HBV co-infection) (evidence rating: AIa)

Efavirenz Position in Guidelines

• Efavirenz-based regimens are relegated to non-integrase inhibitor alternatives, not recommended as first-line therapy. 1
• Efavirenz/TDF/emtricitabine may be considered when integrase inhibitors cannot be used, but only with baseline resistance testing due to transmitted NNRTI resistance risk. 1
• The 2018 guidelines explicitly state that "efavirenz-based treatment was standard initial therapy for many years, but studies have demonstrated higher rates of adverse effects than InSTI-based therapy." 1

Special Clinical Scenarios

Tuberculosis Co-infection

• Dolutegravir (50 mg twice daily) with tenofovir/emtricitabine is recommended during rifamycin-containing TB treatment. 1, 6
• Efavirenz (600 mg) remains an alternative option due to fewer rifampin interactions, but dolutegravir is preferred. 1, 6

Pregnancy

• Dolutegravir plus TAF/emtricitabine (or TDF/emtricitabine) is now the recommended regimen during pregnancy (evidence rating: AIa). 1
• Earlier concerns about neural tube defects with dolutegravir at conception have been addressed, and it is now considered safe. 1
• Efavirenz-based regimens remain safe alternatives during pregnancy but are not preferred. 1, 6

High Viral Load (>100,000 copies/mL)

• Dolutegravir maintains superior efficacy in patients with baseline viral loads >100,000 copies/mL. 2
• Efavirenz demonstrates high efficacy in this population but remains inferior to dolutegravir overall. 1

Key Advantages of Dolutegravir Over Efavirenz

Pharmacologic Benefits

• No pharmacokinetic boosting required (unlike protease inhibitors), reducing drug-drug interactions. 1
• Once-daily dosing without food requirements (unlike rilpivirine). 1
• High barrier to resistance even with inconsistent adherence. 1

Clinical Outcomes

• Faster viral suppression translates to reduced transmission risk and faster immune recovery. 2
• Lower discontinuation rates improve long-term treatment success. 2
• Fewer neuropsychiatric adverse effects improve quality of life. 1

Common Pitfalls to Avoid

When Using Dolutegravir

• Always perform HLA-B*5701 testing before using dolutegravir/abacavir/lamivudine to prevent potentially life-threatening hypersensitivity reactions. 1
• Document HLA-B*5701 positive results prominently in the medical record. 1
• Consider cardiovascular risk when using abacavir-containing regimens in high-risk patients. 1
• Monitor for weight gain, which occurs more frequently with dolutegravir (median 5.0 kg vs 3.0 kg with efavirenz at 96 weeks). 3

When Efavirenz Must Be Used

• Always obtain baseline resistance testing before initiating NNRTI-based regimens due to transmitted resistance risk. 1
• Screen for psychiatric history and avoid in patients with depression or suicidality risk. 1
• Counsel patients about neuropsychiatric adverse effects and rash risk. 1
• Efavirenz requires at least 390 calories for optimal absorption (unlike dolutegravir). 1

Algorithm for Treatment Selection

Start here: Is the patient treatment-naive with HIV-1 infection?

Yes → Choose dolutegravir-based regimen:

• First choice: Bictegravir/TAF/FTC or Dolutegravir + TAF/FTC 1
• If HLA-B*5701 negative: Dolutegravir/abacavir/lamivudine 1
• If HIV RNA <500,000 copies/mL, no HBV, no resistance: Dolutegravir/lamivudine 1

Only use efavirenz if:

• Integrase inhibitors contraindicated or unavailable 1
• TB co-infection where drug interactions preclude dolutegravir dose adjustment 1
• Patient specifically cannot tolerate any integrase inhibitor 1

In all cases: Efavirenz is inferior to dolutegravir for morbidity (adverse effects), mortality (through superior viral suppression), and quality of life (fewer CNS effects). 1, 2