What is the recommended initial treatment regimen for HIV (Human Immunodeficiency Virus)?

Recommended Initial Treatment Regimens for HIV Infection

For initial HIV treatment, integrase strand transfer inhibitor (InSTI)-based regimens are optimal, specifically dolutegravir/abacavir/lamivudine, dolutegravir plus tenofovir alafenamide (TAF)/emtricitabine, elvitegravir/cobicistat/TAF/emtricitabine, or raltegravir plus TAF/emtricitabine. 1

Core Principles of Initial HIV Therapy

• ART is recommended for all HIV-infected individuals with detectable plasma virus, regardless of CD4 cell count, to reduce morbidity and mortality 1
• Initial therapy typically consists of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a third active drug from a different class, usually an InSTI 1
• Treatment should be initiated as soon as possible after diagnosis, with some centers implementing same-day ART initiation 1
• Baseline resistance testing is recommended before starting therapy, though treatment may begin before results are available in some cases 1

Recommended First-Line Regimens

InSTI-Based Regimens (Preferred)

InSTI-based regimens are recommended as first-line therapy due to:

• Higher rates of virologic suppression compared to other regimens 1
• Minimal toxicity and fewer side effects 1
• Lower risk of drug interactions (particularly with dolutegravir and bictegravir) 1
• Higher barrier to resistance (especially dolutegravir) 1

The recommended InSTI-based regimens are:

• Dolutegravir/abacavir/lamivudine (evidence rating AIa) 1

  • Requires HLA-B*5701 testing prior to abacavir use to prevent hypersensitivity reactions 1
  • Demonstrated superiority to efavirenz-based regimens in the SINGLE study 1

• Dolutegravir plus TAF/emtricitabine (evidence rating AIa) 1

  • Good option for patients with or at risk for renal or bone disease 1

• Elvitegravir/cobicistat/TAF/emtricitabine (evidence rating AIa) 1

  • Note that cobicistat is a potent CYP3A4 inhibitor, resulting in more drug interactions than other InSTIs 1

• Raltegravir plus TAF/emtricitabine (evidence rating AIII) 1

  • Higher pill burden (≥3 pills per day) and lower barrier to resistance than dolutegravir 1

Alternative Regimens (When InSTIs are not an option)

If InSTI-based therapy is not possible, the following regimens are recommended:

• Darunavir (boosted) plus TAF (or TDF)/emtricitabine or abacavir/lamivudine (evidence rating AIa) 1
• Efavirenz/TDF/emtricitabine (evidence rating AIa) 1
• Rilpivirine/TAF (or TDF)/emtricitabine (evidence rating AIa) 1

Important Considerations for Regimen Selection

NRTI Backbone Selection

• TAF vs TDF: TAF has fewer renal and bone toxicities compared to TDF, especially when used with pharmacological boosters 1

  • TDF is still effective and generally well-tolerated if TAF is unavailable 1
  • TDF decreases plasma lipid levels more than TAF, though the clinical significance is unknown 1

• Abacavir considerations:

  • HLA-B*5701 testing is mandatory before using abacavir 1
  • Approximately 50% of individuals positive for HLA-B*5701 will experience potentially life-threatening hypersensitivity reactions 1
  • Those who test positive should not receive abacavir and this allergy should be documented in the medical record 1

Special Populations

• Patients with high viral load or low CD4 count: For patients with >100,000 HIV RNA copies/mL or <200 CD4 cells/μL, regimen potency is particularly important as some combinations have suboptimal virologic suppression in this setting 1

• Patients with comorbidities:

  • HBV coinfection: Use TAF or TDF plus lamivudine or emtricitabine as part of the regimen 1
  • HCV coinfection: Select ART regimens without significant drug interactions with HCV therapies 1
  • Renal or bone disease: Avoid TDF in patients with or at risk for kidney disease, osteopenia, or osteoporosis 1

Monitoring and Follow-up

• Regular viral load monitoring is essential to identify treatment failures early and minimize resistance development 1
• Monitor for drug-specific toxicities, particularly during the first few months of therapy 1
• Assess adherence at each visit, as this is critical for treatment success 1

Common Pitfalls to Avoid

• Not testing for HLA-B*5701 before prescribing abacavir-containing regimens 1
• Overlooking drug interactions, particularly with cobicistat-boosted regimens 1
• Delaying ART initiation - early treatment is associated with better outcomes 1
• Using single-agent therapy when modifying a failing regimen, which can lead to resistance 1
• Not considering comorbidities when selecting initial therapy 1