What is the recommended treatment regimen for HIV?

Recommended Treatment Regimen for HIV Infection

The recommended first-line antiretroviral therapy (ART) regimen for HIV treatment is an integrase strand transfer inhibitor (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs), specifically dolutegravir plus tenofovir alafenamide/emtricitabine or abacavir/lamivudine. 1

Initial ART Regimen Selection

Preferred First-Line Regimens:

• InSTI-based regimens (listed alphabetically by InSTI component):
  • Dolutegravir/abacavir/lamivudine (evidence rating AIa) 1
    • Note: HLA-B5701 testing required before abacavir use*
  • Dolutegravir plus tenofovir alafenamide (TAF)/emtricitabine (evidence rating AIa) 1
  • Elvitegravir/cobicistat/TAF/emtricitabine (evidence rating AIa) 1
  • Raltegravir plus TAF/emtricitabine (evidence rating AIII) 1
  • Bictegravir/emtricitabine/tenofovir alafenamide 2

Alternative Regimens (when InSTI is not an option):

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

When to Start ART

ART should be initiated in all HIV-infected individuals, regardless of CD4 cell count (evidence rating AIa) 1. Immediate initiation is recommended as soon as possible after diagnosis, including immediately after diagnosis if the patient is ready (evidence rating BIII) 1.

Monitoring After ART Initiation

1. Initial monitoring: HIV viral load should be checked 1 month after starting or switching regimens 1, 2
2. Follow-up visits: Schedule at intervals of no longer than every 3 months 2
3. Laboratory monitoring:
   • CD4 cell count
   • HIV RNA level
   • Renal function (serum creatinine, estimated creatinine clearance, urine glucose, and urine protein) at least every 6 months 2
   • Hepatic function tests
   • Resistance testing if virologic failure occurs

Management of Treatment Failure

Virologic failure (defined as HIV RNA >200 copies/mL) should be confirmed and addressed promptly 1:

1. Resistance testing is recommended while the patient is taking the failing regimen (evidence rating AIa) or within 4 weeks of stopping (evidence rating AIIa) 1

2. Switch strategies based on failing regimen:

   • After NNRTI failure: Dolutegravir plus 2 NRTIs (with ≥1 active drug determined by genotypic testing) (evidence rating AIa) 1
   • After InSTI failure: A boosted PI plus 2 NRTIs (with ≥1 active NRTI) (evidence rating AIII) 1
   • After raltegravir/elvitegravir failure: Dolutegravir (dosed twice daily) plus at least 1 fully active agent (evidence rating BIII) 1

3. Important cautions:

   • Adding a single active agent to a failing regimen is not recommended (evidence rating AIa) 1
   • For multiclass resistance, use drugs from new classes if available (evidence rating BIII) 1

Switching Strategies in Virologically Suppressed Patients

In patients with viral suppression, switching from a 3-drug regimen to certain 2-drug regimens is appropriate to manage toxicity, intolerance, or improve adherence 1:

• Recommended 2-drug regimens:
  • Dolutegravir/rilpivirine (evidence rating AIa) 1
  • Boosted PI with lamivudine (evidence rating AIa) 1
  • Dolutegravir/lamivudine (evidence rating AIa) 1
  • Long-acting injectable cabotegravir/rilpivirine (evidence rating AIa for every 4 weeks) 1

However, NRTI-reducing strategies have shown higher rates of drug resistance in some studies compared to NRTI-based regimens 3, so careful selection of patients is essential.

Special Considerations

• HBV co-infection: Patients co-infected with HIV and HBV should receive a regimen containing 2 drugs active against HBV, usually TAF or TDF plus lamivudine or emtricitabine (evidence rating AIIa) 1

• Renal impairment: TAF is preferred over TDF for individuals with or at risk of kidney dysfunction (evidence rating BIII) 1

• Bone health concerns: TAF is preferred over TDF for individuals with or at risk of osteopenia or osteoporosis 1

• Monotherapy with boosted PIs or dolutegravir is not recommended (evidence rating AIIa) 1

Common Pitfalls to Avoid

1. Inadequate resistance testing: Always obtain resistance testing before initiating or changing therapy

2. Inappropriate switching: In patients with NRTI resistance mutations, switching from a boosted PI to a regimen with a low genetic barrier to resistance (e.g., NNRTI or raltegravir) is not recommended (evidence rating AIa) 1

3. Drug interactions: Always review co-medications when starting or changing ART regimens 1

4. Suboptimal adherence support: Virologic failure with PIs is rarely due to resistance mutations but often related to adherence issues (evidence rating AIa) 1

5. Ignoring HBV status: Switching to a regimen excluding tenofovir without alternative HBV suppressive therapy in patients with chronic HBV is not recommended 1