What are the different combinations for Antiretroviral Therapy (ART) and their indications?

Antiretroviral Therapy Combinations and Their Indications

The recommended initial antiretroviral therapy (ART) regimen for HIV infection consists of an integrase strand transfer inhibitor (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs), as this combination provides optimal viral suppression with minimal toxicity and excellent survival outcomes. 1

Preferred Initial ART Regimens

InSTI-Based Regimens (First Choice)

• Dolutegravir/abacavir/lamivudine (evidence rating AIa) 2

  • Requires HLA-B*5701 testing before abacavir use
  • Contraindicated in HLA-B*5701 positive patients

• Dolutegravir plus TAF/emtricitabine (evidence rating AIa) 2

  • Preferred for patients with or at risk of kidney or bone disease

• Elvitegravir/cobicistat/TAF/emtricitabine (evidence rating AIa) 2

  • Contains a pharmacokinetic booster (cobicistat)
  • More potential for drug interactions

• Raltegravir plus TAF/emtricitabine (evidence rating AIII) 2

  • Twice-daily dosing may affect adherence

• Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) (evidence rating AIa) 1

  • Single-tablet regimen suitable for rapid initiation

Alternative Regimens (When InSTI Not Suitable)

• Darunavir (boosted) plus TAF/emtricitabine or abacavir/lamivudine (evidence rating AIa) 2

  • Higher barrier to resistance
  • More GI side effects and drug interactions

• Efavirenz/TDF/emtricitabine (evidence rating AIa) 2

  • Associated with CNS side effects
  • Take at bedtime to minimize neuropsychiatric effects

• Rilpivirine/TAF/emtricitabine (evidence rating AIa) 2

  • Must be taken with food
  • Contraindicated with proton pump inhibitors

Special Population Indications

Kidney or Bone Disease

• Avoid TDF-containing regimens (evidence rating BIII) 2
• Prefer TAF-containing regimens or abacavir-based regimens (if HLA-B*5701 negative) 1

Hepatitis B Co-infection

• Must include TDF or TAF plus lamivudine or emtricitabine (evidence rating AIa) 2
• Two drugs active against HBV should be included in the regimen 2
• Avoid 2-drug HIV regimens in HBV co-infected patients 2

Hepatitis C Co-infection

• Choose ART regimens without significant drug interactions with HCV therapies (evidence rating AIIa) 2
• InSTI-based regimens generally have fewer interactions with HCV medications

Pregnancy

• Dolutegravir with TAF/FTC (or TDF/FTC) is recommended 1
• ART should be initiated for maternal health and to prevent perinatal transmission (evidence rating AIa) 2

Two-Drug Regimens

Two-drug regimens are recommended only in specific situations:

• Dolutegravir/rilpivirine for virologically suppressed patients (evidence rating AIa) 2
• Boosted PI with lamivudine for virologically suppressed patients (evidence rating AIIa) 2
• Dolutegravir with lamivudine for treatment-naïve patients without prior resistance (evidence rating AIIa) 2, 3
• Initial 2-drug regimens should be used only when patients cannot take abacavir, TAF, or TDF (evidence rating BIa) 2

Management of Treatment Failure

When virologic failure occurs:

• Resistance testing is recommended while still on failing regimen (evidence rating AIIa) 2
• After NNRTI failure: Switch to dolutegravir plus 2 NRTIs (at least 1 active by genotype) (evidence rating AIa) 2
• After InSTI failure: Switch to a boosted PI plus 2 NRTIs (at least 1 active) (evidence rating AIII) 2
• For raltegravir/elvitegravir resistance: Consider twice-daily dolutegravir plus at least one fully active agent (evidence rating BIII) 2
• For multiclass resistance: Construct regimen using drugs from new classes (evidence rating BIII) 2
• Never add a single active agent to a failing regimen (evidence rating AIa) 2

Monitoring After ART Initiation

• Check viral load 1 month after starting or switching regimens 2
• Assess adherence and tolerability within 6 weeks 1
• Monitor every 3 months for at least 1 year, then every 6 months if viral suppression is maintained 1

Key Considerations for ART Selection

1. Prior resistance testing results
2. Comorbidities (kidney disease, bone disease, cardiovascular risk)
3. Potential drug-drug interactions
4. Pill burden and dosing frequency
5. Genetic barriers to resistance
6. Patient preferences

Common Pitfalls to Avoid

• Not checking HLA-B*5701 status before prescribing abacavir
• Using TDF in patients with kidney dysfunction or bone disease
• Prescribing monotherapy with boosted PIs or dolutegravir (evidence rating AIIa) 2
• Failing to consider drug-drug interactions, especially with PIs and NNRTIs
• Delaying ART initiation - treatment should begin as soon as possible after diagnosis (evidence rating AIa) 2, 1
• Overlooking hepatitis B status before selecting a regimen

The field of HIV treatment continues to evolve, with newer agents and combinations providing improved efficacy, tolerability, and convenience. The current standard of care focuses on early initiation of potent regimens to achieve rapid viral suppression, which benefits both individual health outcomes and prevents HIV transmission.