HIV Treatment for CD4 Count Below 500 cells/µL
Start Antiretroviral Therapy Immediately
All HIV-infected adults with CD4 counts below 500 cells/µL should begin antiretroviral therapy immediately, regardless of viral load or symptoms. This recommendation is based on high-quality evidence showing that early ART reduces mortality by 44-57% and significantly decreases AIDS progression, tuberculosis, and other opportunistic infections 1, 2.
Preferred First-Line Regimens
The following integrase strand transfer inhibitor (InSTI)-based regimens are recommended as first-line therapy:
Top-Tier Options (in order of preference):
Bictegravir/tenofovir alafenamide/emtricitabine (single tablet, once daily) – This is the preferred regimen for most patients because it offers the highest efficacy, best tolerability, strongest resistance barrier, minimal drug interactions, and does not require HLA-B*5701 testing, allowing same-day initiation 1, 3, 4.
Dolutegravir + tenofovir alafenamide/emtricitabine – Provides comparable efficacy with extensive long-term safety data and superior renal and bone safety compared to tenofovir disoproxil fumarate 1, 3, 4.
Dolutegravir/abacavir/lamivudine – May only be used after confirming negative HLA-B*5701 testing and should be avoided in patients with significant cardiovascular risk factors 1, 3.
Critical Pre-Treatment Steps
Laboratory Testing (Do Not Delay Treatment):
Draw blood for HIV-1 RNA viral load, CD4 count, genotypic resistance testing (reverse transcriptase, protease, integrase), hepatitis B and C serology, complete blood count, comprehensive metabolic panel, lipid profile, glucose, and urinalysis before starting ART 1, 3, 5.
The only test that must be completed before prescribing is HLA-B*5701 if planning an abacavir-containing regimen 1, 3, 4.
Do not wait for other laboratory results to return before initiating therapy 1, 5, 4.
Opportunistic Infection Prophylaxis
When CD4 is Below Specific Thresholds:
CD4 < 200 cells/µL: Start trimethoprim-sulfamethoxazole (double-strength, one tablet three times weekly) for Pneumocystis pneumonia prophylaxis; continue until CD4 rises above 200 cells/µL for at least 3 consecutive months 1, 3, 5.
CD4 < 100 cells/µL with positive toxoplasma IgG: The same trimethoprim-sulfamethoxazole regimen provides toxoplasmosis prophylaxis 5.
Mycobacterium avium complex (MAC) prophylaxis is not recommended when effective ART is initiated promptly 1, 5.
Special Timing Considerations for Opportunistic Infections
Tuberculosis Co-infection:
CD4 < 50 cells/µL: Start ART within 2 weeks of beginning TB treatment (unless TB meningitis is present) 1, 5.
CD4 ≥ 50 cells/µL: Start ART within 2-8 weeks of TB treatment initiation 1, 5.
TB meningitis: Defer ART until clinical improvement and CSF parameters normalize, typically 2-4 weeks after starting TB therapy 1, 5.
Compatible ART regimens with rifampin: Use dolutegravir 50 mg twice daily, efavirenz 600 mg once daily, or raltegravir 800 mg twice daily, each with two NRTIs 1, 5, 4.
Do not use bictegravir with rifampin due to significant drug-drug interactions 1, 5, 4.
Cryptococcal Meningitis:
Delay ART for 2-4 weeks after starting antifungal therapy to reduce risk of severe immune reconstitution inflammatory syndrome (IRIS) 1, 5.
Start at 2 weeks if the patient shows clinical improvement, controlled intracranial pressure, negative CSF cultures, and can be closely monitored 1, 5.
Other Opportunistic Infections:
- For most other OIs (Pneumocystis pneumonia, bacterial infections), start ART within 2 weeks of beginning infection-specific therapy 1, 5.
Alternative Regimens When InSTIs Cannot Be Used
Darunavir/ritonavir or darunavir/cobicistat + tenofovir alafenamide/emtricitabine – Preferred protease inhibitor-based option for patients with suspected or confirmed InSTI resistance 1, 3, 4.
Efavirenz/tenofovir disoproxil fumarate/emtricitabine – Reserved for patients with active tuberculosis co-infection due to neuropsychiatric adverse effects 1, 3, 4.
Regimens to Avoid
- Rilpivirine-based combinations are contraindicated when CD4 < 200 cells/µL due to higher risk of virologic failure 3, 4.
Monitoring After ART Initiation
Check HIV-1 RNA viral load at 4-6 weeks after starting ART, then every 4-6 weeks until undetectable (<50 copies/mL) 1, 3, 5.
Monitor CD4 count every 3-6 months during the first year, with less frequent monitoring as immune recovery progresses 1, 3, 5.
Common Pitfalls to Avoid
Do not delay ART while awaiting complete laboratory results (except HLA-B*5701 for abacavir regimens) – this diminishes survival benefits 1, 5, 4.
Do not use tenofovir disoproxil fumarate in patients with creatinine clearance <60 mL/min or osteoporosis – switch to tenofovir alafenamide instead 1, 3, 4.
Do not start ART too early in cryptococcal meningitis without meeting strict clinical criteria – this increases risk of severe IRIS 1, 5.
Do not prescribe abacavir without confirming negative HLA-B*5701 – this can cause potentially fatal hypersensitivity reactions 1, 3, 4.