What is the recommended first‑line antiretroviral therapy and initial management—including baseline laboratory assessment, opportunistic infection prophylaxis, vaccinations, adherence counseling, and follow‑up schedule—for a newly diagnosed adult with HIV infection?

Management of HIV in Newly Diagnosed Adults

First-Line Antiretroviral Therapy

Bictegravir/tenofovir alafenamide/emtricitabine (single-tablet, once daily) is the preferred initial regimen for most newly diagnosed adults because it provides the highest efficacy, best tolerability, strongest barrier to resistance, minimal drug-drug interactions, and does not require HLA-B*5701 testing—enabling same-day treatment initiation. 1, 2, 3

Alternative First-Line Regimens

• Dolutegravir + tenofovir alafenamide/emtricitabine offers comparable efficacy with extensive long-term safety data and superior renal and bone safety compared to tenofovir disoproxil fumarate. 1, 2

• Dolutegravir/abacavir/lamivudine may be used only after confirming a negative HLA-B*5701 result; avoid in patients with significant cardiovascular risk factors, for whom a tenofovir-based regimen is preferred. 1, 2, 3

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

When Integrase Inhibitors Cannot Be Used

• Darunavir/ritonavir (or cobicistat) + tenofovir alafenamide/emtricitabine is the preferred protease-inhibitor option when integrase inhibitors are contraindicated or resistance is suspected. 1, 2, 3

Regimens to Avoid

• Rilpivirine-based regimens are contraindicated when baseline HIV-1 RNA > 100,000 copies/mL or CD4 < 200 cells/µL because of markedly increased virologic failure risk. 1, 2

• Efavirenz + tenofovir disoproxil fumarate/emtricitabine should be reserved exclusively for patients with active tuberculosis co-infection due to neuropsychiatric adverse effects and elevated suicidality risk. 1, 2, 3

Timing of ART Initiation

Start antiretroviral therapy on the day of HIV diagnosis or within 7 days for all patients, regardless of CD4 count, viral load, age, or clinical status. This approach reduces all-cause mortality by 44–57% and markedly lowers progression to AIDS, tuberculosis, and other opportunistic infections. 1, 3

• Do not postpone ART while awaiting routine laboratory results; only HLA-B*5701 testing must be completed before prescribing abacavir. 2, 3

• Eliminate structural barriers (staffing shortages, insurance delays, drug-stock gaps) to enable same-day ART provision at the first clinic visit. 3

Baseline Laboratory Assessment (Draw Before ART, Do Not Delay Treatment)

• HIV-1 RNA viral load 1, 2, 3
• CD4 cell count 1, 2, 3
• Genotypic resistance testing (reverse transcriptase, protease, integrase) 1, 2, 3
• HLA-B*5701 allele testing (mandatory before any abacavir use; start tenofovir-based regimen if results pending) 1, 2, 3
• Hepatitis B surface antigen and hepatitis C antibody 1, 2, 3
• Serum creatinine/eGFR 1, 2
• Complete blood count and comprehensive metabolic panel 2, 3
• Fasting lipid profile and glucose 2, 3
• Pregnancy test for individuals of childbearing potential 2
• Urinalysis for protein and glucose 2, 3

Opportunistic Infection Prophylaxis

Pneumocystis Pneumonia (PCP)

• Initiate trimethoprim-sulfamethoxazole prophylaxis when CD4 < 200 cells/µL and continue until CD4 rises above 200 cells/µL for at least 3 consecutive months. 1, 3

Mycobacterium Avium Complex (MAC)

• Primary MAC prophylaxis is no longer recommended when effective ART is started promptly, as early treatment markedly lowers MAC incidence. 1, 3

Cryptococcal Disease

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

Timing of ART with Opportunistic Infections

• For most opportunistic infections, initiate ART within 2 weeks of starting infection-specific therapy. 1, 3

• For tuberculosis with CD4 ≥ 50 cells/µL, initiate ART within 2–8 weeks of starting TB treatment. 1, 3

• For tuberculosis with CD4 < 50 cells/µL, initiate ART within 2 weeks of starting TB treatment to reduce mortality. 1, 3

• For cryptococcal meningitis, delay ART for 4–6 weeks after starting antifungal therapy to lower the risk of severe immune reconstitution inflammatory syndrome (IRIS). 1, 3

• For newly diagnosed malignancy, initiate ART immediately while carefully managing drug-drug interactions. 1, 3

Special Population Considerations

Tuberculosis Co-infection

• Dolutegravir 50 mg twice daily, efavirenz 600 mg daily, or raltegravir 800 mg twice daily (each with two NRTIs) are recommended when receiving rifamycin-based TB therapy. 1, 3

• Bictegravir is contraindicated with rifampin due to clinically significant drug-drug interactions. 1, 3

• Boosted protease inhibitors are reserved for cases where integrase-inhibitor or efavirenz-based options are unsuitable; substitute rifabutin 150 mg daily for rifampin to avoid interactions. 1, 3

Pregnancy

• Dolutegravir + tenofovir alafenamide/emtricitabine is the preferred regimen during pregnancy. 1, 2, 3

• Bictegravir/tenofovir alafenamide/emtricitabine is an acceptable alternative. 2, 3

• If a protease inhibitor is required, use darunavir 600 mg + ritonavir 100 mg twice daily (not once daily). 1, 3

• Atazanavir/ritonavir, raltegravir, and efavirenz are acceptable alternatives when combined with tenofovir disoproxil fumarate + emtricitabine or lamivudine. 1, 3

Renal Impairment or Osteoporosis

• Avoid tenofovir disoproxil fumarate; use tenofovir alafenamide instead to reduce nephrotoxicity and bone loss. 2, 3

• Tenofovir alafenamide is not recommended when creatinine clearance < 30 mL/min. 3

• Bictegravir/tenofovir alafenamide/emtricitabine can be used in patients with creatinine clearance ≥ 30 mL/min, making it the first non-boosted integrase-inhibitor regimen suitable for moderate renal impairment. 4

Hepatitis B Co-infection

• Start an ART regimen that includes tenofovir (alafenamide or disoproxil fumarate) together with lamivudine or emtricitabine to provide dual activity against HBV. 2, 3, 4

• 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. 3

Advanced Immunosuppression (CD4 ≤ 35 cells/µL)

• Use the same preferred integrase-inhibitor regimens (bictegravir- or dolutegravir-based); rilpivirine must be avoided. 2, 5

• Initiate PCP prophylaxis when CD4 < 200 cells/µL. 5

Monitoring After Treatment Initiation

Viral Load Monitoring

• Measure HIV-1 RNA at 4–6 weeks after ART start to assess initial response. 2, 3, 5

• Continue testing every 4–6 weeks until viral load < 50 copies/mL (target by 24 weeks). 2, 3

• Once suppressed, monitor every 3 months during the first year, then every 6 months after 1–2 years of sustained suppression. 2, 3

CD4 Monitoring

• Measure CD4 count every 3–6 months during the first year. 2, 5

• After the first year, test every 6 months until CD4 rises above 250 cells/µL for at least one year. 2

• CD4 monitoring may be discontinued if viral suppression is maintained and CD4 > 500 cells/µL for 2 years. 3

Additional Monitoring

• Monitor eGFR, urinalysis, glycosuria, and proteinuria at ART initiation, after any regimen change, and every 6 months once HIV-RNA is stable. 3

Adherence Counseling and Follow-Up

• Provide proactive adherence counseling at every visit to achieve rapid viral suppression and reduce morbidity. 5

• Close clinical follow-up (at least monthly during the first three months) is advised to monitor for opportunistic infections, IRIS, and treatment tolerability. 5

Common Pitfalls to Avoid

• Failing to perform HLA-B*5701 testing before prescribing abacavir can lead to potentially fatal hypersensitivity reactions; always confirm a negative result or choose a tenofovir-based regimen. 2, 3

• Delaying ART initiation while awaiting laboratory results eliminates the survival benefit of early treatment; start ART promptly unless the patient is not ready to commit. 2, 3

• Using rilpivirine in patients with high viral load (> 100,000 copies/mL) or low CD4 counts (< 200 cells/µL) results in markedly higher virologic failure rates. 1, 2

• Prescribing tenofovir disoproxil fumarate to patients with renal disease (CrCl < 60 mL/min) or osteoporosis leads to avoidable nephrotoxicity and bone loss; switch to tenofovir alafenamide. 2, 3

• Starting NNRTI-based regimens or abacavir for same-day ART initiation delays therapy because they require baseline resistance testing and HLA-B*5701 results; tenofovir-based integrase-inhibitor regimens are preferred. 2, 3

• Co-administering bictegravir with rifampin is contraindicated due to significant drug-drug interactions; use alternative agents. 1, 3