What is the recommended initial management for a newly diagnosed HIV‑positive adult, including first‑line antiretroviral therapy regimen, baseline laboratory evaluation, opportunistic infection prophylaxis, follow‑up schedule, and adjustments for pregnancy?

HIV Management in Newly Diagnosed Adults

Start antiretroviral therapy immediately on the day of HIV diagnosis—or within 7 days at most—regardless of CD4 count, viral load, or clinical status, and use bictegravir/tenofovir alafenamide/emtricitabine as the preferred first-line regimen for most patients. 1

Timing of ART Initiation

• Initiate ART as soon as possible after diagnosis, including same-day start if the patient is ready to commit to treatment. This approach reduces mortality by 44–57% and significantly decreases AIDS progression, tuberculosis, and opportunistic infections. 1
• Remove all structural barriers (staffing shortages, insurance delays, drug-stock gaps) to enable ART at the first clinic visit. 1
• Do not wait for baseline laboratory results before starting treatment—only HLA-B*5701 must be confirmed before prescribing abacavir-containing regimens. 2, 3

Baseline Laboratory Evaluation (Obtain but Do Not Delay Treatment)

• Required baseline tests include:
  • HIV-1 RNA viral load 2, 3
  • CD4 cell count 2, 3
  • Genotypic resistance testing (reverse transcriptase, protease, integrase) 2, 3
  • HLA-B*5701 allele testing (mandatory before any abacavir use) 1, 2, 3
  • Hepatitis B surface antigen and hepatitis C antibody 2, 3
  • Serum creatinine/eGFR 2, 3
  • Complete blood count, comprehensive metabolic panel, fasting lipids, glucose 3
  • Pregnancy test for individuals of childbearing potential 2, 3
  • Urinalysis for glucose and protein 3

First-Line Antiretroviral Regimens

Preferred Regimen for Most Patients

• Bictegravir/tenofovir alafenamide/emtricitabine (single-tablet, once daily) provides the highest efficacy, best tolerability, strongest barrier to resistance, minimal drug interactions, and no requirement for HLA-B*5701 testing—making it ideal for rapid/same-day initiation. 2, 4, 5, 6
• This regimen achieved 92.4% virologic suppression at 48 weeks in treatment-naïve adults with no treatment-emergent resistance and significantly less nausea than dolutegravir/abacavir/lamivudine (10% vs 23%). 4

Equally Effective Alternatives

• Dolutegravir + tenofovir alafenamide/emtricitabine offers comparable efficacy with extensive long-term safety data and superior renal/bone safety compared to tenofovir disoproxil fumarate. 2, 3
• Dolutegravir/abacavir/lamivudine (single tablet) may be used only after confirming negative HLA-B*5701 testing; avoid in patients with cardiovascular risk factors—use a tenofovir-based regimen instead. 1, 2, 3

Alternative Regimens When Integrase Inhibitors Cannot Be Used

• Darunavir/cobicistat + tenofovir alafenamide/emtricitabine is the preferred protease-inhibitor option when integrase-inhibitor resistance is suspected, particularly after long-acting cabotegravir PrEP exposure. 2, 3
• Darunavir/ritonavir + tenofovir alafenamide/emtricitabine provides an alternative boosting strategy. 1, 2
• Raltegravir + tenofovir alafenamide/emtricitabine requires twice-daily dosing and has a lower resistance barrier than dolutegravir or bictegravir. 1, 2, 3

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. 2, 3
• Efavirenz + tenofovir disoproxil fumarate/emtricitabine should be reserved only for active tuberculosis co-infection because of neuropsychiatric adverse effects and elevated suicidality risk. 1, 2, 3
• Do not use NNRTIs or abacavir for rapid/same-day ART initiation because baseline resistance testing and HLA-B*5701 results are required first. 2, 3

Special Population Adjustments

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 needed, use darunavir 600 mg + ritonavir 100 mg twice daily (not once daily). 1, 3
• Atazanavir/ritonavir, raltegravir, and efavirenz are also acceptable options when combined with tenofovir disoproxil fumarate/emtricitabine or tenofovir disoproxil fumarate/lamivudine. 1

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

Hepatitis B Co-infection

• Use regimens containing tenofovir alafenamide or tenofovir disoproxil fumarate plus emtricitabine or lamivudine to provide dual activity against HBV. 2, 3
• Avoid dolutegravir/lamivudine two-drug regimen in HBV co-infection. 2
• Entecavir may be added for HBV treatment but should be avoided if HIV-RNA is not suppressed because it can select for HIV drug resistance. 3

Tuberculosis Co-infection

• Dolutegravir (50 mg twice daily), efavirenz (600 mg/day), or raltegravir (800 mg twice daily) plus 2 nucleoside reverse transcriptase inhibitors are recommended for patients receiving rifamycin-based TB treatment. 1
• Bictegravir with rifampin is not recommended due to drug-drug interactions. 1
• For TB with CD4 ≥ 50 cells/µL, initiate ART within 2–8 weeks of starting TB treatment. 1
• For TB with CD4 < 50 cells/µL, initiate ART within 2 weeks of starting TB treatment to reduce mortality. 1, 3
• Boosted protease inhibitors are recommended only if integrase inhibitor–based or efavirenz-based regimens are not options; substitute rifabutin (150 mg/day) for rifampin if a protease inhibitor must be used. 1

Cryptococcal Meningitis

• Delay ART initiation 4–6 weeks after starting antifungal therapy to minimize risk of severe immune reconstitution inflammatory syndrome (IRIS). 1, 3

Other Opportunistic Infections

• Initiate ART within 2 weeks of starting treatment for most opportunistic infections. 1, 3

Cancer Diagnosis

• Initiate ART immediately in the setting of new cancer diagnosis with attention to drug-drug interactions. 1

Opportunistic Infection Prophylaxis

• Start trimethoprim-sulfamethoxazole for primary Pneumocystis pneumonia prophylaxis when CD4 < 200 cells/µL; continue until CD4 > 200 cells/µL for at least 3 months. 3
• Mycobacterium avium complex (MAC) prophylaxis is not required when effective ART is started promptly because early treatment markedly lowers MAC incidence. 3
• Cryptococcal prophylaxis is not recommended in high-resource settings with low disease prevalence. 3

Follow-Up and Monitoring Schedule

Viral Load Monitoring

• Obtain HIV-1 RNA at 4–6 weeks after ART initiation to assess initial response. 2, 3
• Continue testing every 4–6 weeks until viral load is < 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, 3
• After the first year, test every 6 months until CD4 rises above 250 cells/µL for at least one year. 2, 3
• CD4 monitoring may be discontinued if viral suppression is maintained and CD4 > 500 cells/µL for 2 years. 3

Safety Monitoring

• Assess adherence and tolerability at each visit. 3
• Monitor for drug-specific toxicities, including renal function, bone density, and metabolic parameters. 2, 3

Common Pitfalls and How to Avoid Them

• Failing to perform HLA-B*5701 testing before prescribing abacavir can lead to potentially fatal hypersensitivity reactions—always confirm negative status or use a tenofovir-based regimen. 1, 2, 3
• Delaying ART initiation while awaiting laboratory results reduces the benefits of early treatment—start ART immediately unless the patient is not ready to commit. 1, 2, 3
• 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—avoid this regimen in these populations. 2, 3
• Prescribing tenofovir disoproxil fumarate to patients with renal disease (CrCl < 60 mL/min) or osteoporosis causes avoidable nephrotoxicity and bone loss—switch to tenofovir alafenamide. 2, 3
• Starting dolutegravir/lamivudine two-drug regimen without confirming HIV RNA < 500,000 copies/mL, absence of lamivudine resistance, and no HBV co-infection can lead to treatment failure. 2
• Overlooking drug interactions, particularly with cobicistat-boosted regimens or in patients taking rifampin, can compromise efficacy or cause toxicity. 2, 3
• Not initiating Pneumocystis pneumonia prophylaxis when CD4 < 200 cells/µL increases risk of life-threatening infection. 3