What is the recommended first‑line antiretroviral regimen for an adult newly diagnosed with HIV who has no contraindications?

Best HIV Medications for Treatment-Naive Adults

For adults newly diagnosed with HIV without contraindications, start bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) as a single-tablet regimen—it offers the highest efficacy, best tolerability, and strongest resistance barrier among first-line options. 1, 2

Primary Recommended Regimens (Integrase Inhibitor-Based)

The three generally recommended first-line regimens are all integrase strand transfer inhibitor (InSTI)-based combinations with AIa evidence ratings 1:

• Bictegravir/TAF/emtricitabine (single tablet) – Preferred for most patients due to superior tolerability, once-daily dosing, minimal drug interactions, and high genetic barrier to resistance 1, 2
• Dolutegravir + TAF/emtricitabine – Equally effective with extensive long-term safety data; available as single tablet or separate pills 1, 2
• Dolutegravir/abacavir/lamivudine (single tablet) – Requires mandatory HLA-B*5701 testing before use to prevent potentially life-threatening hypersensitivity reactions 1, 2

Why INSTIs Are Superior

INSTIs achieve faster viral suppression than older regimens—81.3% of patients on INSTI-based therapy achieved viral suppression at 3 months versus 67.3% on efavirenz-based therapy 3. By 7 years, both maintain excellent suppression rates above 92% 3. Second-generation INSTIs (dolutegravir, bictegravir) have extremely low rates of resistance development in treatment-naive patients 4, 5, 6.

Alternative Regimens When INSTIs Cannot Be Used

If the preferred regimens are unavailable or contraindicated, use these alternatives (all AIa evidence) 1:

• Darunavir/cobicistat + TAF/emtricitabine – Best protease inhibitor option with high resistance barrier; particularly useful when INSTI resistance is suspected 1, 2, 7
• Darunavir/ritonavir + TAF/emtricitabine – Alternative boosting with ritonavir instead of cobicistat 1
• Elvitegravir/cobicistat/TAF/emtricitabine – Another INSTI option but has more drug interactions due to cobicistat 1, 2
• Raltegravir + TAF/emtricitabine – First-generation INSTI requiring twice-daily dosing 1

Regimens to Avoid or Use With Caution

• Rilpivirine-based regimens are contraindicated if baseline HIV RNA >100,000 copies/mL or CD4 count <200/μL due to high virologic failure risk 1, 8
• Efavirenz/TDF/emtricitabine – Reserve for tuberculosis co-infection; causes neuropsychiatric side effects and increased suicidality risk 1
• NNRTIs and abacavir should not be used for rapid ART start due to need for baseline resistance testing and HLA-B*5701 results 1

Critical Pre-Treatment Testing (Do Not Delay ART Initiation)

Start ART immediately at diagnosis—draw labs but begin treatment before results return 1, 8:

• HIV-1 RNA viral load 1, 8
• CD4 cell count 1, 8
• Genotypic resistance testing (reverse transcriptase, protease, integrase) 1, 8
• HLA-B*5701 allele testing (mandatory before abacavir; use tenofovir-based regimen until results available) 1, 2
• Hepatitis B surface antigen and hepatitis C antibody 1, 8
• Serum creatinine/estimated creatinine clearance 1, 8
• Pregnancy test for individuals of childbearing potential 1

Special Population Considerations

Renal Impairment or Osteoporosis

• Avoid tenofovir disoproxil fumarate (TDF)—use tenofovir alafenamide (TAF) instead for better renal and bone safety 1, 2, 7

Hepatitis B Co-Infection

• Must include tenofovir (TAF or TDF) plus emtricitabine or lamivudine in the regimen 8, 2
• Do not use dolutegravir/lamivudine two-drug regimen 2

Pregnancy

• Dolutegravir + TAF/emtricitabine is preferred; bictegravir/TAF/emtricitabine is an alternative 2
• Note: Earlier concerns about neural tube defects with dolutegravir at conception have been re-evaluated, but discuss risks/benefits 1

Advanced Immunosuppression (CD4 ≤35 cells/μL)

• Same preferred regimens apply (bictegravir/TAF/FTC, dolutegravir-based) 8
• Absolutely avoid rilpivirine in this population 8
• Initiate Pneumocystis pneumonia prophylaxis if CD4 <200/μL 1, 8

High Baseline Viral Load (>100,000 copies/mL)

• High viral load predicts treatment failure (HR 2.2) 9
• Use preferred INSTI regimens; avoid rilpivirine entirely 1

Tuberculosis Co-Infection

• Efavirenz/TDF/emtricitabine has extensive experience with rifampin co-administration 1
• Rifampin cannot be used with bictegravir, dolutegravir/lamivudine, elvitegravir/cobicistat, or rilpivirine 2

Monitoring After Treatment Initiation

Viral load monitoring schedule 1, 8, 2:

• At 4-6 weeks after starting ART to assess initial response 8, 2
• Every 4-6 weeks until HIV RNA <50 copies/mL (target by 24 weeks) 8, 2
• Every 3 months once suppressed for first year 2
• Every 6 months after sustained suppression for 1-2 years 1, 2

CD4 monitoring 1, 8:

• Every 3-6 months during first year 8
• Every 6 months until >250/μL for 1 year, then can stop if virus remains suppressed 1

Common Pitfalls to Avoid

• Not testing HLA-B*5701 before prescribing abacavir—can cause fatal hypersensitivity reaction 1, 2
• Delaying ART initiation while waiting for lab results—start immediately unless patient not ready to commit 1
• Using rilpivirine in patients with high viral load or low CD4 counts—guaranteed higher failure rates 1, 8
• Prescribing TDF to patients with renal disease or osteoporosis—use TAF instead 1, 2
• Missing hepatitis B co-infection—requires specific NRTI backbone 8, 2
• Overlooking drug interactions with cobicistat-boosted regimens—particularly problematic 2

Emerging Considerations

Weight gain has been observed with second-generation INSTIs (dolutegravir, bictegravir), though long-term clinical implications remain under study 5, 6. This does not change their status as preferred agents given overwhelming efficacy and tolerability advantages 5, 6.