What is the recommended algorithm for initiating and managing antiretroviral therapy in a newly diagnosed HIV‑1‑positive adult (or adolescent), including baseline laboratory evaluation, first‑line regimen selection, adjustments for renal impairment, hepatitis B co‑infection, pregnancy, resistance mutations, and follow‑up monitoring?

Algorithm for Managing HIV-1 Positive Patients

Immediate Action: Start ART on Day of Diagnosis

Initiate antiretroviral therapy immediately upon HIV diagnosis—or within 7 days at most—regardless of CD4 count, viral load, age, or clinical status. This approach reduces all-cause mortality by 44–57% and markedly lowers AIDS progression, tuberculosis, and opportunistic infections. 1

• Same-day ART initiation is feasible, safe, and achieves faster viral suppression (median 1.8 months) compared to delayed initiation (4.3 months). 2, 3
• Eliminate structural barriers (insurance delays, drug-stock gaps, staffing shortages) to enable ART provision at the first clinic visit. 1
• Do not postpone treatment while awaiting laboratory results—only HLA-B*5701 testing must be completed before prescribing abacavir. 4, 5

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Baseline Laboratory Evaluation (Draw Before Starting, But Do Not Wait)

Obtain the following tests before initiating ART, but start treatment immediately without waiting for results:

• HIV-1 RNA viral load 4, 5
• CD4 cell count 4, 5
• Genotypic resistance testing for reverse transcriptase, protease, and integrase 4, 5
• HLA-B*5701 allele testing (mandatory before any abacavir use; start a tenofovir-based regimen if results are pending) 4, 5
• Hepatitis B surface antigen and hepatitis C antibody 5, 1
• Complete blood count, comprehensive metabolic panel, liver function tests 1
• Serum creatinine/eGFR 5, 1
• Fasting lipid profile and glucose 1
• Pregnancy test for individuals of childbearing potential 5
• Urinalysis for glucose and protein 1

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First-Line Regimen Selection

Preferred Regimen for Most Adults (Ranked by Strength of Evidence)

1. Bictegravir/tenofovir alafenamide/emtricitabine (single tablet, once daily)

• This is the preferred first-line regimen because it offers the highest efficacy, best tolerability, strongest barrier to resistance, minimal drug-drug interactions, and does not require HLA-B*5701 testing—making it ideal for same-day initiation. 5, 1

2. Dolutegravir + tenofovir alafenamide/emtricitabine (once daily)

• Equally effective with extensive long-term safety data and superior renal/bone safety compared to tenofovir disoproxil fumarate (TDF). 5, 1

3. Dolutegravir/abacavir/lamivudine (single tablet, once daily)

• Use only after confirming negative HLA-B*5701 test. Avoid in patients with cardiovascular risk factors; prefer a tenofovir-based regimen instead. 4, 5, 1

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Alternative Regimens When Integrase Inhibitors Cannot Be Used

• Darunavir/cobicistat (or ritonavir) + tenofovir alafenamide/emtricitabine: Preferred protease-inhibitor option when integrase-inhibitor resistance is suspected or contraindicated. 5, 1
• Raltegravir + tenofovir alafenamide/emtricitabine: First-generation integrase inhibitor requiring twice-daily dosing with lower resistance barrier than dolutegravir/bictegravir. 5, 1
• Elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine: Higher potential for drug-drug interactions due to cobicistat. 5, 1

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Regimens to Avoid or Use With Extreme Caution

• Rilpivirine-based regimens are contraindicated when baseline HIV-1 RNA > 100,000 copies/mL or CD4 < 200 cells/µL due to markedly increased virologic failure risk. 5, 1
• Efavirenz + tenofovir disoproxil fumarate/emtricitabine should be reserved exclusively for patients with active tuberculosis co-infection; it carries neuropsychiatric adverse effects and elevated suicidality risk. 5, 1
• NNRTIs and abacavir should not be used for rapid/same-day ART initiation because they require baseline resistance testing and HLA-B*5701 results. 4, 5

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Special Population Adjustments

Renal Impairment or Osteoporosis

• Avoid tenofovir disoproxil fumarate (TDF) in patients with creatinine clearance < 60 mL/min or osteopenia/osteoporosis. 5, 1
• Use tenofovir alafenamide (TAF) instead for superior renal and bone safety. 5, 1
• TAF is not recommended when creatinine clearance < 30 mL/min. 1
• Monitor eGFR, urinalysis, glycosuria, and proteinuria at ART initiation, after regimen changes, and every 6 months once HIV-RNA is stable. 1

Pregnancy

• Preferred regimen: Dolutegravir + tenofovir alafenamide/emtricitabine. 5, 1
• Acceptable alternative: Bictegravir/tenofovir alafenamide/emtricitabine. 5, 1
• If a protease inhibitor is required, use darunavir 600 mg + ritonavir 100 mg twice daily (once-daily dosing is insufficient during pregnancy). 5, 1
• Initiate ART immediately in pregnant individuals to protect maternal health and prevent vertical transmission. 1

Hepatitis B Co-infection

• Start a regimen containing tenofovir alafenamide (or TDF) plus lamivudine or emtricitabine for dual HIV/HBV activity. 1
• Entecavir may be added for HBV treatment but should be avoided if HIV-RNA is not suppressed, as it can select for HIV drug resistance. 1

Hepatitis C Co-infection

• Choose ART drugs with no significant pharmacokinetic interactions with direct-acting HCV agents. 1

Tuberculosis Co-infection

For patients receiving rifampin-based TB therapy:

• Efavirenz + tenofovir disoproxil fumarate/emtricitabine is the recommended backbone due to extensive clinical experience and compatible drug-interaction profile. 5, 1
• Alternative options: Dolutegravir 50 mg twice daily or raltegravir 800 mg twice daily, each combined with two NRTIs. 1
• Bictegravir should not be co-administered with rifampin due to clinically significant drug-drug interactions. 1

Timing of ART initiation with TB:

• CD4 < 50 cells/µL: Start ART within 2 weeks of TB treatment initiation to reduce mortality. 1
• CD4 ≥ 50 cells/µL: Start ART 2–8 weeks after beginning TB treatment to balance efficacy with IRIS risk. 1

Advanced Immunosuppression (CD4 ≤ 35 cells/µL)

• Use the same preferred integrase-inhibitor regimens (bictegravir- or dolutegravir-based). 5
• Avoid rilpivirine entirely. 5
• Initiate Pneumocystis pneumonia prophylaxis with trimethoprim-sulfamethoxazole when CD4 < 200 cells/µL; continue until CD4 > 200 cells/µL for ≥ 3 months. 4, 1

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

• Use preferred integrase-inhibitor regimens. 5
• Avoid rilpivirine entirely due to high virologic failure risk. 5

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Opportunistic Infection Management and ART Timing

• Most opportunistic infections: Start ART within 2 weeks of beginning OI treatment. 4, 1
• Cryptococcal meningitis: Delay ART 4–6 weeks after starting antifungal therapy to minimize severe IRIS risk. 4, 1
• Newly diagnosed malignancy: Start ART immediately while managing drug-drug interactions. 4, 1
• Primary MAC prophylaxis is no longer recommended when effective ART is initiated promptly. 4, 1

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Monitoring After ART Initiation

Viral Load Monitoring

• Obtain HIV-1 RNA at 4–6 weeks after ART start to assess initial response. 5, 1
• Continue testing every 4–6 weeks until viral load is < 50 copies/mL (target by 24 weeks). 5
• Once suppressed, monitor every 3 months during the first year, then every 6 months after 1–2 years of sustained suppression. 5, 1

CD4 Monitoring

• Measure CD4 count every 3–6 months during the first year. 5
• After the first year, test every 6 months until CD4 rises above 250 cells/µL for at least one year. 5
• CD4 monitoring may be discontinued after CD4 > 500 cells/µL for 2 years with viral suppression. 1

Safety Monitoring

• Monitor eGFR, urinalysis, glycosuria, and proteinuria at ART initiation, after regimen changes, and every 6 months once HIV-RNA is stable. 1
• Assess adherence and tolerability at each visit. 1

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Common Pitfalls and How to Avoid Them

• Failing to perform HLA-B*5701 testing before prescribing abacavir can precipitate potentially fatal hypersensitivity reactions; always confirm a negative result or choose a tenofovir-based regimen. 5, 1
• Delaying ART while awaiting laboratory results diminishes survival and disease-progression benefits; start ART promptly unless the patient is not ready to commit. 4, 5, 1
• Using rilpivirine in patients with high viral load (>100,000 copies/mL) or low CD4 (<200 cells/µL) results in markedly higher virologic failure rates. 5, 1
• Prescribing TDF to patients with renal disease (CrCl < 60 mL/min) or osteoporosis leads to avoidable nephrotoxicity and bone loss; switch to TAF. 5, 1
• Starting NNRTIs or abacavir for same-day initiation delays therapy because baseline resistance and HLA-B*5701 testing are required; opt for tenofovir-based integrase-inhibitor regimens instead. 4, 5
• Co-administering bictegravir with rifampin causes clinically significant drug-drug interactions; use efavirenz, dolutegravir 50 mg twice daily, or raltegravir 800 mg twice daily instead. 1