What is the recommended treatment regimen for HIV based on viral load and CD4 (Cluster of Differentiation 4) count labs?

HIV Treatment Based on Viral Load and CD4 Count

All HIV-infected adults with detectable viremia should start antiretroviral therapy immediately, regardless of CD4 count or viral load level. 1

When to Initiate Treatment

The decision to start ART is no longer based on CD4 thresholds—treatment is universally recommended for all patients with established HIV infection and detectable plasma virus 1. This represents a paradigm shift from earlier guidelines that used CD4 count cutoffs of 200,350, or 500 cells/μL 2, 3.

Key initiation principles:

• Start ART as soon as possible after HIV diagnosis, ideally at the first clinic visit 1, 4
• In acute HIV infection, initiate treatment immediately to reduce viral reservoir seeding 1
• Even patients with CD4 counts >500 cells/μL benefit from immediate treatment, with 57% reduction in severe morbidity compared to deferred therapy 5
• Never defer treatment based on high CD4 counts—two-thirds of serious clinical events occur in patients with CD4 >500 cells/μL 5

Recommended Initial Regimens

First-Line Regimens for Most Patients

The preferred approach is an integrase strand transfer inhibitor (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs) 1:

Top-tier options (2024 guidelines):

• Bictegravir/TAF/emtricitabine (single tablet) 1
• Dolutegravir plus tenofovir/emtricitabine (TAF or TDF formulation) 1
• Dolutegravir/lamivudine (two-drug regimen)—only if HIV RNA <500,000 copies/mL, no lamivudine resistance, and no hepatitis B co-infection 1

Alternative InSTI-based regimens:

• Dolutegravir/abacavir/lamivudine (requires HLA-B*5701 testing first) 1
• Raltegravir plus TAF/emtricitabine 1
• Elvitegravir/cobicistat/TAF/emtricitabine 1

When InSTI Regimens Are Not an Option

If InSTI-based therapy cannot be used, alternative anchors include:

• Boosted darunavir (with ritonavir or cobicistat) plus TAF/emtricitabine or TDF/emtricitabine 1
• Efavirenz/TDF/emtricitabine 1
• Rilpivirine/TAF/emtricitabine (only if baseline HIV RNA <100,000 copies/mL and CD4 >200 cells/μL) 1

Critical Pre-Treatment Considerations

Mandatory Testing Before Starting ART

Draw these labs before the first ART dose, but do not delay treatment while waiting for results 1:

• HIV-1 RNA viral load 1
• CD4 cell count 1
• Genotypic resistance testing for reverse transcriptase and protease 1
• HLA-B*5701 allele testing (if considering abacavir) 1
• Hepatitis A, B, and C serologies 1
• Serum chemistries, estimated creatinine clearance, complete blood count 1
• Fasting lipid profile 1
• Pregnancy test in persons of childbearing potential 1

Special Situations Requiring Regimen Modification

Patients with drug resistance mutations:

• If NRTI resistance is present, avoid bictegravir/TAF/emtricitabine and dolutegravir-based regimens 6
• Use boosted darunavir plus TAF/emtricitabine when InSTI or NRTI resistance is suspected 6
• Integrase resistance testing is not routine unless source virus is from someone with InSTI treatment failure 1

Patients with renal impairment:

• Avoid tenofovir disoproxil fumarate (TDF) in those with or at risk for kidney disease 1, 6
• Prefer tenofovir alafenamide (TAF) over TDF for better renal and bone safety profile 1, 6

Patients with hepatitis B co-infection:

• Must include tenofovir (TAF or TDF) plus lamivudine or emtricitabine 1
• Never use dolutegravir/lamivudine two-drug regimen in hepatitis B co-infection 1

Pregnant individuals:

• TAF/emtricitabine plus dolutegravir is preferred 1
• Darunavir (600 mg) plus ritonavir (100 mg) twice daily with TAF/emtricitabine is an alternative 1
• Bictegravir/TAF/emtricitabine may be continued if pregnancy is discovered while on this regimen 1

Patients who acquired HIV while on PrEP:

• If breakthrough infection occurred on TAF/FTC or TDF/FTC PrEP, obtain genotype before starting treatment 1
• Start a three-drug regimen (preferably dolutegravir or bictegravir plus tenofovir/emtricitabine) while awaiting results 1
• If breakthrough occurred on cabotegravir PrEP, obtain InSTI genotype; use boosted darunavir plus tenofovir/emtricitabine if InSTI resistance is suspected 1

Monitoring After Treatment Initiation

Viral Load Monitoring

Check HIV RNA every 4-6 weeks after starting or changing ART until undetectable 1:

• Target is HIV RNA <50 copies/mL by 24 weeks 1
• Once suppressed for 1 year, monitor every 3 months 1
• After 2 years of suppression with stable adherence, can extend to every 6 months 1

If viral load remains >50 copies/mL at 24 weeks or rebounds after suppression:

• Repeat assay within 4 weeks to confirm virologic failure 1
• Assess adherence barriers 1
• Obtain resistance testing while patient is still on failing regimen 1

CD4 Count Monitoring

CD4 monitoring frequency depends on baseline count and viral suppression 1:

• **If baseline CD4 <200 cells/μL:** Check every 3-4 months until viral load suppressed and CD4 >350 cells/μL for 1 year 1
• Once CD4 >500 cells/μL with sustained viral suppression for ≥2 years: CD4 monitoring is optional and can be discontinued 1

Prophylaxis Based on CD4 Count

Pneumocystis pneumonia prophylaxis:

• Initiate primary prophylaxis if CD4 <200 cells/μL 1

Mycobacterium avium complex (MAC):

• Primary MAC prophylaxis is no longer recommended if effective ART is initiated promptly 1

Common Pitfalls to Avoid

Do not delay ART initiation waiting for resistance testing results—start treatment immediately and modify regimen if needed when results return 1, 4

Do not use NNRTIs or abacavir for rapid same-day ART start—these require specific testing (resistance and HLA-B*5701) that takes days to result 1

Do not use two-drug regimens (dolutegravir/lamivudine) for rapid ART initiation—this requires confirmation of viral load <500,000 copies/mL, absence of lamivudine resistance, and negative hepatitis B serology 1

Do not start ART at different CD4 thresholds based on patient characteristics—the evidence supports immediate treatment for all, with even greater benefits in resource-limited settings where tuberculosis and bacterial infections are prevalent 3