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

Recommended Initial HIV Treatment Regimens

For individuals newly diagnosed with HIV, the recommended initial antiretroviral therapy (ART) regimen should consist of an integrase strand transfer inhibitor (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs), specifically bictegravir/tenofovir alafenamide/emtricitabine, dolutegravir/abacavir/lamivudine, or dolutegravir plus tenofovir alafenamide/emtricitabine. 1

When to Start ART

ART should be initiated as soon as possible after diagnosis, including immediately after diagnosis if the patient is ready to commit to treatment. This approach is supported by strong evidence showing improved clinical outcomes and reduced transmission risk 1.

Key considerations for ART initiation:

• Start ART regardless of CD4 cell count in all viremic patients with established HIV infection 1
• Initiate ART as soon as possible in acute HIV infection 1
• Before starting ART, obtain baseline labs including:
  • HIV-1 RNA level
  • CD4 cell count
  • HIV genotype for NRTI, NNRTI, and PI resistance
  • HLA-B*5701 testing (if considering abacavir)
  • Tests to exclude active viral hepatitis
  • Basic chemistry panel

However, treatment may be started before all results are available to expedite care 1.

First-Line Regimen Options

Generally Recommended Initial Regimens (in alphabetical order by InSTI component)

1. Bictegravir/TAF/emtricitabine (evidence rating AIa) 1
2. Dolutegravir/abacavir/lamivudine (evidence rating AIa) 1
   • Requires negative HLA-B*5701 testing before use
   • Not recommended for patients with high cardiovascular risk
3. Dolutegravir plus TAF/emtricitabine (evidence rating AIa) 1

These InSTI-based regimens are preferred due to:

• Superior virologic efficacy
• Better tolerability
• Lower rates of treatment discontinuation
• Higher barrier to resistance

Alternative Regimens (when preferred options are not available)

• Darunavir (boosted) plus TAF/emtricitabine or abacavir/lamivudine
• Elvitegravir/cobicistat/TAF/emtricitabine
• Raltegravir plus TAF/emtricitabine
• Rilpivirine/TAF/emtricitabine (only if HIV RNA <100,000 copies/mL and CD4 >200 cells/μL)

Special Considerations

Tenofovir Formulation Choice

• Tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF) for patients with or at risk for kidney or bone disease 1
• TDF is not recommended for individuals with osteopenia or osteoporosis 1
• If TAF is not available, TDF remains an effective option for patients without kidney or bone concerns

Abacavir Considerations

• HLA-B*5701 testing must be performed before abacavir use; those testing positive should not receive abacavir 1
• Consider tenofovir-containing regimens rather than abacavir for patients with or at high risk for cardiovascular disease 1

Hepatitis B Co-infection

For patients co-infected with HIV and hepatitis B virus:

• Use regimens containing TDF or TAF plus lamivudine or emtricitabine 1
• Avoid 2-drug regimens that do not adequately treat hepatitis B

Pregnancy

• HIV-infected pregnant women should initiate ART for their own health and to reduce the likelihood of HIV transmission to their infant 1
• Note: There are concerns about potential teratogenicity with dolutegravir when initiated before conception 1

Monitoring After ART Initiation

• Check HIV viral load 1 month after starting treatment
• Continue monitoring every 3-4 months until viral suppression is achieved
• For stable patients with sustained viral suppression, monitoring can be extended to every 6 months

Common Pitfalls to Avoid

1. Delaying ART initiation while waiting for all baseline test results - this can lead to missed opportunities for early viral suppression
2. Using NNRTIs or abacavir for rapid ART start before baseline test results are available - these may be problematic if resistance or HLA-B*5701 positivity is present
3. Failing to test for HLA-B*5701 before prescribing abacavir-containing regimens
4. Using TDF in patients with renal impairment or bone disease - TAF is preferred in these populations
5. Initiating 2-drug regimens as first-line therapy - these are only recommended in rare situations when patients cannot take abacavir, TAF, or TDF

The evidence strongly supports that early initiation of an InSTI-based regimen with two NRTIs provides the best outcomes for mortality, morbidity, and quality of life for people living with HIV.