What is a recommended first-line antiretroviral treatment regimen for patients with Human Immunodeficiency Virus (HIV)?

Recommended First-Line Antiretroviral Treatment Regimens for HIV

For most patients with HIV, the recommended first-line antiretroviral therapy (ART) regimen consists of an integrase strand transfer inhibitor (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs), specifically dolutegravir plus tenofovir alafenamide/emtricitabine or abacavir/lamivudine. 1

Optimal Initial Regimens

The following InSTI-based regimens are recommended as first-line therapy (in alphabetical order):

• Dolutegravir/abacavir/lamivudine (evidence rating AIa) 2, 1
• Dolutegravir plus tenofovir alafenamide (TAF)/emtricitabine (evidence rating AIa) 2, 1
• Elvitegravir/cobicistat/TAF/emtricitabine (evidence rating AIa) 2, 1
• Raltegravir plus TAF/emtricitabine (evidence rating AIII) 2, 1

Rationale for InSTI-Based Regimens

InSTI-based regimens are preferred due to:

• High rates of viral suppression
• Minimal toxicity
• Low pill burden
• Few drug interactions 2, 1

Dolutegravir and bictegravir specifically offer a high barrier to resistance compared to other InSTIs 2, 3. In clinical trials:

• Dolutegravir plus abacavir/lamivudine was superior to efavirenz/TDF/emtricitabine in the SINGLE study 2
• Dolutegravir was superior to ritonavir-boosted darunavir in the FLAMINGO study 2
• Elvitegravir/cobicistat was superior to atazanavir/ritonavir in women in the WAVES study 2
• Raltegravir was superior to atazanavir/ritonavir or darunavir/ritonavir in the AIDS Clinical Trials Group 5257 study 2

Choice of NRTI Components

When selecting the NRTI backbone:

• Tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF) for patients with or at risk of kidney dysfunction or bone disease (osteopenia or osteoporosis) (evidence rating BIII) 2, 1, 4
• Abacavir requires HLA-B*5701 testing prior to use; those who test positive should not receive abacavir (evidence rating AIa) 2, 1
• Tenofovir disoproxil fumarate (TDF) remains an effective and generally well-tolerated option if TAF is unavailable 2

Alternative Regimens

When an InSTI-based regimen is not an option, the following regimens are recommended:

• Darunavir (boosted) plus TAF (or TDF)/emtricitabine or abacavir/lamivudine (evidence rating AIa) 2, 1
• Efavirenz/TDF/emtricitabine (evidence rating AIa) 2, 1
• Rilpivirine/TAF (or TDF)/emtricitabine (evidence rating AIa) 2, 1

Two-Drug Initial Therapy

Dolutegravir/lamivudine has emerged as an effective two-drug regimen for initial therapy 2, 5, 6. However, it should be used only in select patients:

• HIV RNA <500,000 copies/mL
• CD4 count >200 cells/μL
• No HBV co-infection
• No resistance to either component 5

Special Populations

HIV/HBV Co-infection

Patients co-infected with HIV and HBV should receive a regimen containing:

• TDF or TAF (evidence rating AIa)
• Lamivudine or emtricitabine
• A third component from another class 2, 1

HIV/HCV Co-infection

Patients co-infected with HIV and HCV should start an ART regimen with drugs that do not have significant interactions with HCV therapies (evidence rating AIIa) 2, 1

Timing of ART Initiation

• ART should be started as soon as possible after diagnosis 1
• For patients with opportunistic infections, ART should be started within 2 weeks after initiation of treatment for most opportunistic infections (evidence rating AIa) 2
• For patients with tuberculosis and CD4 count <50 cells/μL, ART should be started within 2 weeks after tuberculosis treatment initiation 2

Monitoring

• HIV viral load should be checked 1 month after starting or switching regimens
• Regular monitoring of renal function is recommended, especially with tenofovir-containing regimens 1, 4
• Baseline resistance testing is recommended for all patients, though therapy may be initiated prior to results in some cases 2

Common Pitfalls and Caveats

• Drug interactions: Always check for potential interactions, especially with PIs and NNRTIs 1
• Weight gain: TAF is associated with greater weight gain than TDF 2
• Abacavir concerns: Lingering concerns exist regarding a link between abacavir and increased risk of myocardial infarction 2
• Resistance testing: Important before starting therapy, particularly for NNRTIs which have higher rates of transmitted resistance compared to InSTIs and PIs 2
• Discontinuation in HBV co-infection: Severe acute exacerbations of hepatitis B can occur when discontinuing tenofovir-containing regimens 4

By following these evidence-based recommendations, clinicians can optimize outcomes for patients with HIV, reducing morbidity and mortality while improving quality of life.