How should I start antiretroviral therapy (ART) in a newly diagnosed treatment‑naïve adult with HIV and normal renal function, including baseline labs and first‑line regimen selection?

How to Start Antiretroviral Therapy in Newly Diagnosed HIV

Start antiretroviral therapy immediately on the day of HIV diagnosis—or within 7 days at most—for all treatment-naïve adults, regardless of CD4 count or viral load. This approach reduces all-cause mortality by 44–57% and markedly lowers AIDS progression, tuberculosis, and opportunistic infections. 1

Baseline Laboratory Testing

Draw baseline labs before starting ART, but do not delay treatment while awaiting results. The only exception is HLA-B*5701 testing when an abacavir-containing regimen is planned. 1

Required Tests (Draw Before ART, Start Treatment Immediately)

• HIV-1 RNA viral load 1
• CD4 cell count 1
• Genotypic resistance testing for NRTI, NNRTI, protease inhibitor, and integrase 1
• Hepatitis B and C serologies 1
• Complete blood count and comprehensive metabolic panel 1
• Fasting lipid profile and glucose 1
• Urinalysis for protein and glucose 1
• Pregnancy test (if applicable) 2

Mandatory Pre-Treatment Test

• HLA-B*5701 allele testing must be completed and negative before prescribing any abacavir-containing regimen to prevent potentially fatal hypersensitivity reactions. 1, 2

First-Line Regimen Selection

Preferred Regimen for Most Adults

Bictegravir/tenofovir alafenamide (TAF)/emtricitabine (single tablet, once daily) is the preferred first-line regimen because it offers the highest efficacy, best tolerability, strongest resistance barrier, minimal drug-drug interactions, and does not require HLA-B*5701 testing—enabling same-day start. 1, 2

Equally Recommended Alternatives

• Dolutegravir + TAF/emtricitabine (once daily) provides comparable efficacy with extensive long-term safety data and superior renal and bone safety versus tenofovir disoproxil fumarate (TDF). 1, 2

• Dolutegravir/abacavir/lamivudine (once daily) may be used only after confirming negative HLA-B*5701 and should be avoided in patients with significant cardiovascular risk factors; use a tenofovir-based regimen instead. 1, 2

Alternative Regimens When Preferred Options Unavailable

• Darunavir/ritonavir (or cobicistat) + TAF (or TDF)/emtricitabine for patients with contraindications to integrase inhibitors. 1

• Raltegravir + TAF/emtricitabine requires twice-daily dosing and has a lower resistance barrier than dolutegravir or bictegravir. 1, 2

• Rilpivirine/TAF/emtricitabine only if baseline HIV-RNA <100,000 copies/mL **and** CD4 >200 cells/µL; otherwise, virologic failure risk is markedly increased. 1, 2

Regimens to Avoid for Rapid Start

Do not use NNRTIs or abacavir for same-day initiation because they require baseline resistance testing and HLA-B*5701 results, which delay therapy. Use tenofovir-based integrase inhibitor regimens instead. 1, 2, 3

Special Populations and Circumstances

Renal or Bone Disease

Avoid TDF in patients with creatinine clearance <60 mL/min or with osteopenia/osteoporosis; use TAF instead to reduce nephrotoxicity and bone loss. 2

Pregnancy

• Dolutegravir + TAF/emtricitabine is the preferred regimen during pregnancy. 2
• If a protease inhibitor is required, use darunavir 600 mg + ritonavir 100 mg twice daily (not once daily). 1, 2
• Atazanavir/ritonavir, raltegravir, and efavirenz are acceptable alternatives. 1

Hepatitis B Co-infection

Start an ART regimen that includes TDF or TAF together with lamivudine or emtricitabine to provide dual activity against HBV. 2

Timing with Opportunistic Infections

Tuberculosis Co-infection

For CD4 <50 cells/µL (without TB meningitis): Start ART within 2 weeks of beginning TB therapy to reduce mortality. 1, 4, 2, 3

For CD4 ≥50 cells/µL: Start ART within 2–8 weeks of TB therapy initiation. 1, 4, 2, 3

For TB meningitis: Defer ART until clinical and CSF improvement, typically 2–4 weeks after TB treatment begins. 4

ART Regimens Compatible with Rifampin

When rifampin is part of TB treatment, use:

• Dolutegravir 50 mg twice daily, or 1, 4, 2
• Efavirenz 600 mg once daily, or 1, 4, 2
• Raltegravir 800 mg twice daily 1, 4, 2

Each combined with two NRTIs.

Bictegravir must not be co-administered with rifampin due to significant drug-drug interactions. 1, 4, 2

Cryptococcal Meningitis

Delay ART for 4–6 weeks after starting antifungal therapy to lower the risk of severe immune reconstitution inflammatory syndrome (IRIS). 1, 4, 2, 3

Start ART at 2 weeks only if the patient shows clinical improvement, controlled intracranial pressure, negative CSF cultures, and can be closely monitored. 4

Other Opportunistic Infections

For most other OIs (e.g., Pneumocystis pneumonia, bacterial infections): Start ART within 2 weeks of beginning infection-specific therapy. 1, 4, 3

Malignancy

Initiate ART immediately upon cancer diagnosis while carefully reviewing potential drug-drug interactions. 1, 4, 3

Opportunistic Infection Prophylaxis

Pneumocystis Pneumonia (PCP)

Start trimethoprim-sulfamethoxazole (double-strength, one tablet three times weekly) for CD4 <200 cells/µL and continue until CD4 rises above 200 cells/µL for at least 3 consecutive months. 1, 4, 2, 3

Mycobacterium Avium Complex (MAC)

Primary MAC prophylaxis is no longer recommended when effective ART is started promptly. 1, 4, 2, 3

Cryptococcal Disease

Prophylaxis is not recommended in high-resource settings with low disease prevalence. 1, 4, 3

Post-Initiation Monitoring

• HIV-1 RNA viral load: Check at 4–8 weeks after starting ART, then every 3 months until undetectable (<50 copies/mL) for at least one year, then every 6 months. 4, 2

• CD4 count: Measure every 3–6 months during the first year to assess immune recovery. 4, 2

Common Pitfalls to Avoid

Do not delay ART while awaiting complete laboratory results (except HLA-B*5701 for abacavir); postponement eliminates the survival benefit of early treatment. 1, 2, 3

Do not prescribe abacavir without confirming negative HLA-B*5701 to prevent potentially fatal hypersensitivity reactions. 1, 2

Do not start ART too early in cryptococcal meningitis without meeting strict clinical criteria (improvement, controlled ICP, negative CSF cultures), as this raises severe IRIS risk. 4, 2

Do not use TDF in patients with CrCl <60 mL/min or osteoporosis; switch to TAF to avoid nephrotoxicity and bone loss. 2

Eliminate structural barriers (staffing shortages, insurance delays, drug-stock gaps) that prevent same-day ART initiation at the first clinic visit. 1, 2, 3