What is the initial recommended treatment regimen for Antiretroviral Therapy (ART) in Human Immunodeficiency Virus (HIV)?

Initial Recommended Treatment Regimen for HIV

The initial recommended antiretroviral therapy (ART) regimen for HIV infection is an integrase strand transfer inhibitor (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs), specifically dolutegravir plus tenofovir alafenamide/emtricitabine or abacavir/lamivudine. 1, 2

Preferred First-Line Regimens

InSTI-based regimens are optimal for initial therapy due to their superior efficacy, tolerability, and high barrier to resistance. The recommended initial ART regimens (in alphabetical order by InSTI component) include:

1. Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC)
2. Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC)
3. Dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC)
4. Elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/c/TAF/FTC)
5. Raltegravir plus tenofovir alafenamide/emtricitabine (RAL + TAF/FTC)

Two-Drug Regimen Option

Dolutegravir/lamivudine (DTG/3TC) is the single recommended 2-drug regimen for initial ART (evidence rating: AIa) 1. However, it should not be used if:

• Lamivudine resistance is detected on HIV genotyping
• HIV RNA level is ≥500,000 copies/mL
• Hepatitis B co-infection is present
• During pregnancy (limited data)
• CD4+ cell count is below 200/μL (limited data)

Special Considerations

Nucleoside/Nucleotide Backbone

Tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) with emtricitabine (FTC) or lamivudine (3TC) remain the recommended NRTI components of an initial ART regimen 1. TAF is preferred over TDF for individuals with or at risk of kidney dysfunction or bone disease 2.

Abacavir Considerations

When using abacavir-containing regimens, HLA-B*5701 testing must be performed prior to initiation. Patients who test positive should not receive abacavir due to risk of hypersensitivity reaction 2.

Pregnancy

For pregnant women with HIV, dolutegravir with TAF/FTC (or TDF/XTC if TAF/FTC is not available) is the recommended ART regimen for maternal health and to prevent perinatal and sexual transmission 1.

Suspected Resistance

In cases where InSTI resistance is suspected before resistance testing results are available (particularly with prior exposure to long-acting cabotegravir as PrEP), boosted darunavir-containing regimens are recommended 1.

HIV/HBV Co-infection

Patients co-infected with HIV and HBV should receive a regimen containing two drugs active against HBV, usually TAF or TDF plus lamivudine or emtricitabine, in addition to a third ART drug 2.

Monitoring After Initiation

After starting ART, adherence and tolerability should be assessed within 6 weeks, along with HIV RNA level. HIV RNA suppression may take up to 24 weeks, though InSTI-based regimens typically achieve faster viral suppression. Once HIV RNA is below 50 copies/mL, monitoring every 3 months is recommended for at least 1 year, then every 6 months if viral suppression is maintained 1.

Common Pitfalls to Avoid

1. Not checking for HLA-B*5701 before using abacavir - This can lead to potentially life-threatening hypersensitivity reactions
2. Using DTG/3TC in patients with high viral loads - Two-drug regimens may be less effective in patients with HIV RNA ≥500,000 copies/mL
3. Not considering drug-drug interactions - Particularly important with boosted regimens (containing ritonavir or cobicistat)
4. Initiating ART without baseline resistance testing - Though therapy can be started before results are available in some cases
5. Not considering hepatitis B status - Two-drug regimens should be avoided in patients with HBV co-infection

The evidence strongly supports that early initiation of ART with these recommended regimens leads to improved morbidity, mortality, and quality of life outcomes for patients with HIV infection.