What is the recommended first‑line antiretroviral therapy regimen for an adult with HIV and a CD4 count of 35 cells/µL?

Recommended ART Regimen for CD4 Count of 35 cells/µL

For an adult with HIV and a CD4 count of 35 cells/µL, initiate an integrase strand transfer inhibitor (InSTI)-based regimen immediately, with bictegravir/tenofovir alafenamide/emtricitabine or dolutegravir plus tenofovir alafenamide/emtricitabine as the preferred first-line options. 1

Immediate Treatment Initiation

• Start antiretroviral therapy immediately at the first clinic visit, regardless of the low CD4 count—treatment should never be delayed for this patient with advanced immunosuppression 1
• The CD4 count of 35 cells/µL indicates severe immunocompromise and high risk for opportunistic infections, making urgent ART initiation critical for reducing morbidity and mortality 1

Preferred First-Line Regimens

Top-tier InSTI-based options include:

• Bictegravir/tenofovir alafenamide/emtricitabine (single-tablet regimen with high efficacy and favorable tolerability profile) 2, 1
• Dolutegravir plus tenofovir alafenamide/emtricitabine (highly effective with excellent resistance barrier) 2, 1
• Dolutegravir/abacavir/lamivudine (alternative single-tablet option, but requires negative HLA-B*5701 testing first) 3, 2

Why InSTI-Based Regimens Are Preferred

• InSTI-based regimens demonstrate superior virological efficacy and tolerability compared to protease inhibitor or NNRTI-based alternatives 2, 1
• These regimens achieve viral suppression rapidly, which is critical at this low CD4 count 1
• Dolutegravir has shown superiority over efavirenz and ritonavir-boosted darunavir in clinical trials 4

Critical Regimens to AVOID at CD4 <200 cells/µL

Do NOT use rilpivirine-based regimens (rilpivirine/tenofovir alafenamide/emtricitabine or rilpivirine/tenofovir disoproxil fumarate/emtricitabine) in this patient, as rilpivirine is contraindicated when CD4 count is <200 cells/µL due to increased risk of virologic failure 3

Alternative Regimens if InSTI Not Suitable

If InSTI-based therapy cannot be used:

• Darunavir/cobicistat/tenofovir alafenamide/emtricitabine (protease inhibitor-based with high barrier to resistance) 3, 2
• Efavirenz plus tenofovir disoproxil fumarate/emtricitabine (particularly if tuberculosis co-infection present, though higher neuropsychiatric side effects) 3

Essential Pre-Treatment Steps

Draw labs immediately but do NOT delay treatment while waiting for results: 1

• HIV-1 RNA viral load
• CD4 cell count (already known as 35 cells/µL)
• Genotypic resistance testing (HIV RT-pro genotype and integrase genotype if considering InSTI) 3, 1
• HLA-B*5701 allele testing (only if considering abacavir-containing regimen) 3, 1
• Hepatitis B and C screening 3
• Pregnancy test if applicable 1
• Baseline renal function (creatinine clearance) 5

Opportunistic Infection Prophylaxis

With CD4 count of 35 cells/µL, immediately initiate:

• Pneumocystis jirovecii pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) double-strength daily or three times weekly 1
• Screen for and treat active opportunistic infections before or concurrent with ART initiation 1
• Primary MAC prophylaxis is no longer routinely recommended if effective ART is initiated promptly 1

Monitoring Schedule

Intensive early monitoring is essential: 3, 1

• Check HIV RNA at 4-6 weeks after starting ART, then every 4-6 weeks until undetectable 1
• Target: HIV RNA <50 copies/mL by 24 weeks 1
• CD4 count every 3-6 months initially, with frequency decreasing as immune reconstitution occurs 3, 1
• Monitor for immune reconstitution inflammatory syndrome (IRIS), which is more common with advanced immunosuppression 1

Special Considerations for Low CD4 Count

• Patients with CD4 <50 cells/µL are at highest risk for opportunistic infections and IRIS 1
• Ensure close clinical follow-up in the first 3 months after ART initiation 1
• Address adherence support proactively, as this patient needs rapid viral suppression 3