What is the recommended antiretroviral therapy (ART) regimen for a newly diagnosed person living with Human Immunodeficiency Virus (HIV)?

Antiretroviral Therapy for Newly Diagnosed HIV

Start antiretroviral therapy immediately upon HIV diagnosis with an integrase strand transfer inhibitor (INSTI)-based regimen, preferably bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC), dolutegravir plus TAF/FTC, or dolutegravir/abacavir/lamivudine if HLA-B*5701 negative. 1, 2, 3

When to Start Treatment

• Initiate ART as soon as possible after diagnosis, including same-day start if the patient is ready to commit to treatment, regardless of CD4 count or viral load. 1, 2
• Treatment should not be delayed for laboratory results except HLA-B*5701 testing if using abacavir-containing regimens. 1, 2
• Structural barriers preventing same-day or first-visit initiation must be removed. 1, 2

Recommended First-Line Regimens

Preferred Regimens (in order of preference):

1. Bictegravir/TAF/emtricitabine - highest efficacy, favorable side effect profile, high barrier to resistance 1, 3
2. Dolutegravir plus TAF/emtricitabine - strong resistance profile, highly effective 1, 3
3. Dolutegravir/abacavir/lamivudine - requires HLA-B*5701 testing first (must be negative to use) 1, 3

Alternative Regimens (when preferred options unavailable):

• Raltegravir plus TAF/emtricitabine 1
• Darunavir (boosted with ritonavir or cobicistat) plus TAF/emtricitabine - particularly when INSTI resistance suspected 1, 3
• Elvitegravir/cobicistat/TAF/emtricitabine 1

Critical Pre-Treatment Considerations

Mandatory Testing Before Starting:

• HLA-B*5701 must be negative before using any abacavir-containing regimen to prevent potentially life-threatening hypersensitivity reactions. 1, 2, 3
• Draw baseline HIV-1 RNA, CD4 count, resistance testing (genotype for NRTI, NNRTI, PI), hepatitis B and C screening, and basic chemistries, but do not delay treatment waiting for results. 1, 2

Regimens to AVOID for Rapid Start:

• Do not use NNRTIs (efavirenz, rilpivirine) or abacavir for same-day/rapid start due to baseline testing requirements. 1, 2
• Dolutegravir/lamivudine (2-drug regimen) is not appropriate for rapid start - requires confirmation of HIV RNA <500,000 copies/mL, no resistance, and no hepatitis B. 3

Special Populations and Circumstances

Tuberculosis Co-infection:

• For active TB with CD4 <50 cells/μL: Start ART within 2 weeks of TB treatment initiation 1, 4
• For active TB with CD4 ≥50 cells/μL: Start ART within 2-8 weeks of TB treatment 1, 4
• Use dolutegravir 50 mg twice daily (not once daily) plus 2 NRTIs with rifamycin-based TB regimens 1, 4
• Bictegravir cannot be used with rifampin due to drug-drug interactions. 1

Pregnancy:

• Dolutegravir plus TAF/emtricitabine is the preferred regimen during pregnancy 1, 3, 4
• Initiate immediately for maternal health and prevention of vertical transmission. 1
• Alternative options include atazanavir/ritonavir, darunavir/ritonavir, raltegravir, or efavirenz (all with TDF/FTC or TDF/3TC backbone). 1

Hepatitis B Co-infection:

• Must use regimens containing TAF or TDF plus emtricitabine or lamivudine 1, 3, 4
• Do not use dolutegravir/lamivudine 2-drug regimen in hepatitis B co-infection. 3

Renal Impairment:

• Avoid tenofovir disoproxil fumarate (TDF); use tenofovir alafenamide (TAF) instead 1, 3, 4
• TAF has significantly fewer renal and bone toxicities compared to TDF. 3

Osteoporosis/Bone Disease:

• Prefer TAF over TDF due to reduced bone toxicity. 1, 3

Opportunistic Infections:

• For most OIs: Start ART within 2 weeks of diagnosis 1, 2
• For cryptococcal meningitis: DELAY ART for 4-6 weeks after starting antifungal therapy to reduce risk of immune reconstitution inflammatory syndrome (IRIS). 1, 2
• For newly diagnosed malignancy: Start ART immediately with attention to drug-drug interactions. 1, 2

Prophylaxis Requirements:

• Start Pneumocystis pneumonia prophylaxis if CD4 <200 cells/μL 1, 2
• MAC prophylaxis is no longer recommended if effective ART is initiated. 1, 2
• Cryptococcal prophylaxis not recommended in high-resource settings. 1, 2

Common Pitfalls to Avoid

• Never delay ART waiting for complete laboratory results (except HLA-B*5701 if using abacavir). 1, 2
• Never use abacavir without confirming HLA-B*5701 negative status - can cause life-threatening hypersensitivity. 1, 2, 3
• Never start ART early in cryptococcal meningitis - wait 4-6 weeks to reduce IRIS risk. 1, 2
• Never use standard dolutegravir dosing (50 mg once daily) with rifampin - must increase to 50 mg twice daily. 1, 4
• Never overlook drug interactions with cobicistat-boosted regimens or in patients taking rifampin. 3, 4
• Never use rilpivirine for rapid start or if HIV RNA >100,000 copies/mL or CD4 <200 cells/μL. 1

Monitoring After Initiation

• Measure HIV RNA at 4-6 weeks to assess initial virologic response. 3, 4
• Monitor every 3 months until viral suppression maintained for at least 1 year. 3
• After 1 year of suppression, reduce monitoring to every 6 months. 3
• Regularly assess for drug-specific toxicities (renal function for TDF, hepatotoxicity, metabolic parameters). 3, 4