What is the recommended initial antiretroviral therapy and comprehensive management plan for a newly diagnosed HIV‑infected adult, including regimen selection, baseline assessments, opportunistic infection prophylaxis, vaccinations, monitoring, and considerations for renal impairment, pregnancy, and treatment failure?

HIV Management in Newly Diagnosed Adults

All newly diagnosed HIV-infected adults should start antiretroviral therapy immediately—on the day of diagnosis or within 7 days—regardless of CD4 count or viral load, using an integrase strand transfer inhibitor (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs) as the preferred first-line regimen. 1

When to Start ART

• Initiate ART immediately for all viremic patients with established HIV infection, regardless of CD4 cell count. 2 This recommendation is based on evidence showing 44-57% reduction in severe morbidity (including death, AIDS diseases, and non-AIDS cancers) with early versus deferred treatment. 3

• Start ART as soon as possible in acute HIV infection to achieve faster viral suppression and reduce transmission risk. 2

• Do not delay ART initiation while awaiting complete laboratory results—only HLA-B*5701 testing must be completed before prescribing abacavir. 1, 4 All other baseline tests should be drawn but treatment should not be postponed. 1

Baseline Laboratory Assessment

Obtain the following tests before starting ART, but do not wait for results to initiate treatment (except HLA-B*5701 if planning abacavir use): 1, 4

• HIV-1 RNA viral load
• CD4+ cell count
• Genotypic resistance testing (reverse transcriptase, protease, integrase)
• HLA-B*5701 allele testing (mandatory before any abacavir use—approximately 50% of positive patients will experience potentially life-threatening hypersensitivity reactions) 1, 4, 5
• Hepatitis B surface antigen and hepatitis C antibody
• Complete blood count (CBC)
• Comprehensive metabolic panel (CMP) including serum creatinine/eGFR
• Fasting lipid profile and glucose
• Urinalysis for glucose and protein
• Pregnancy test for individuals of childbearing potential 1

Recommended First-Line Regimens

Preferred Regimens (InSTI + 2 NRTIs)

Bictegravir/tenofovir alafenamide (TAF)/emtricitabine is the single most preferred regimen for most newly diagnosed adults due to: 1, 4

• Highest efficacy and tolerability
• Strongest barrier to resistance
• Minimal drug interactions
• Once-daily single-tablet dosing
• Superior renal and bone safety compared to TDF

Alternative equally effective first-line options include:

• Dolutegravir + TAF/emtricitabine—comparable efficacy with extensive long-term safety data 2, 1, 4

• Dolutegravir/abacavir/lamivudine—requires confirmed negative HLA-B*5701 testing; avoid in patients with cardiovascular risk factors (use tenofovir-based regimen instead) 2, 1, 4

• Elvitegravir/cobicistat/TAF/emtricitabine—higher potential for drug-drug interactions due to cobicistat 2, 1

• Raltegravir + TAF/emtricitabine—first-generation InSTI with lower resistance barrier and higher pill burden than dolutegravir/bictegravir 2, 1

When InSTIs Cannot Be Used

Darunavir (boosted with ritonavir or cobicistat) + TAF/emtricitabine or abacavir/lamivudine is the preferred protease inhibitor-based option when InSTI resistance is suspected or contraindicated. 2, 1, 4

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, 1, 4

• Efavirenz/TDF/emtricitabine should be reserved only for patients with active tuberculosis co-infection; it carries neuropsychiatric adverse effects and elevated suicidality risk. 2, 1, 4

• Do not use NNRTIs or abacavir for same-day ART initiation because they require baseline resistance testing and HLA-B*5701 results that delay therapy. 1, 4

Rapid (Same-Day) ART Initiation

For same-day start, use tenofovir-containing InSTI regimens: 1

• Bictegravir/TAF/emtricitabine
• Dolutegravir + TAF/emtricitabine
• Raltegravir + TAF or TDF/emtricitabine

Same-day ART initiation is safe, acceptable, and achieves significantly faster viral suppression (median 1.8 months vs. 4.3 months with delayed start). 6, 7 Among patients starting ART at the first visit, 79% achieved viral suppression by week 12,82% by week 24, and 88% by week 48. 7

Special Population Considerations

Renal Impairment or Bone Disease

• Avoid tenofovir disoproxil fumarate (TDF) in patients with or at risk for kidney disease (CrCl <60 mL/min) or osteopenia/osteoporosis. 2, 1, 4

• Preferentially use TAF to reduce nephrotoxicity and bone loss. 2, 1, 4

• TDF should be dose-adjusted when CrCl <60 mL/min and discontinued if renal function worsens, particularly with proximal tubular dysfunction. 2

• TAF is not recommended when CrCl <30 mL/min. 2

• Monitor eGFR, urinalysis, glycosuria, and albuminuria/proteinuria at ART initiation, when changing regimens, and every 6 months once HIV RNA is stable. 2

Pregnancy

• Pregnant individuals should initiate ART immediately for their own health and to reduce vertical transmission. 2

• Recommended regimens include:

  • Dolutegravir + TAF/emtricitabine (preferred) 1, 4
  • Bictegravir/TAF/emtricitabine (acceptable alternative) 1, 4
  • Darunavir 600 mg + ritonavir 100 mg twice daily (not once daily) 1

• Dolutegravir has early-conception teratogenicity concerns but remains an acceptable option per current guidelines. 1

Hepatitis B Co-infection

• Initiate ART containing TDF or TAF plus lamivudine or emtricitabine. 2

• Avoid dolutegravir/lamivudine two-drug regimen in HBV co-infection. 4

• Entecavir may be used for HBV treatment but should be avoided if HIV RNA is not suppressed, as it can select for drug-resistant HIV. 2

Hepatitis C Co-infection

• Start an ART regimen with drugs that do not have significant drug interactions with HCV therapies. 2

Tuberculosis Co-infection

Timing of ART initiation depends on CD4 count and TB site: 1

TB Type	CD4 Count	ART Timing	Rationale
Non-meningeal TB	<50 cells/µL	Within 2 weeks of TB therapy start	Reduces mortality in severely immunocompromised patients [1]
Non-meningeal TB	≥50 cells/µL	Within 2–8 weeks of TB therapy start	Balances efficacy with IRIS risk [1]
TB meningitis	<50 cells/µL	Within 2 weeks (expert consensus)	Close IRIS monitoring essential [1]

• Efavirenz/TDF/emtricitabine is recommended for TB co-infection due to extensive experience with concurrent rifampin therapy. 1, 4

• Rifampin cannot be used with bictegravir/TAF/FTC, dolutegravir/lamivudine, elvitegravir/cobicistat, or rilpivirine. 4

Cryptococcal Meningitis

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

Other Opportunistic Infections

• For most other OIs, initiate ART within 2 weeks of starting OI treatment. 1

• For newly diagnosed malignancies, start ART immediately while managing drug-drug interactions. 1

Opportunistic Infection Prophylaxis

Pneumocystis Pneumonia (PCP)

• Start trimethoprim-sulfamethoxazole prophylaxis for all patients with CD4 <200 cells/µL. 1

• Continue prophylaxis even after starting ART until CD4 rises above 200 cells/µL for at least 3 months. 1

Mycobacterium Avium Complex (MAC)

• Primary MAC prophylaxis is NOT recommended when effective ART is initiated immediately, as early treatment markedly lowers MAC incidence. 1

Cryptococcus

• Cryptococcal prophylaxis is NOT recommended in high-resource settings with low disease prevalence. 1

Monitoring After ART Initiation

Viral Load Monitoring

• Measure HIV-1 RNA at 4–6 weeks after starting ART to assess initial response. 1, 4

• Continue testing every 4–6 weeks until viral load is <50 copies/mL (target by 24 weeks). 1

• Once suppressed, monitor every 3 months during the first year, then every 6 months after 1–2 years of sustained suppression. 1, 4

CD4 Monitoring

• Measure CD4 count every 3–6 months during the first year. 1

• After the first year, test every 6 months until CD4 >250 cells/µL for at least 1 year with viral suppression. 1

• Discontinue CD4 monitoring after CD4 >500 cells/µL for 2 years with maintained viral suppression. 1

Additional Monitoring

• Assess adherence and tolerability at each visit—adherence is critical for treatment success. 1, 4, 5

• Monitor for drug-specific toxicities, particularly during the first few months. 4, 5

Management of Treatment Failure

Virologic failure is defined as:

• Inability to achieve viral suppression (<50 copies/mL) by 24 weeks
• Confirmed detectable viral load after previous suppression

When treatment failure occurs: 1, 4

• Obtain resistance testing while the patient is still on the failing regimen.

• Switch to a regimen containing at least two (preferably three) fully active agents guided by resistance testing. 1

• Select drugs from different pharmacologic classes than those in the failing regimen. 1

• InSTIs with high resistance barriers (dolutegravir, bictegravir) are preferred for second-line use when they were not part of the first-line regimen. 1

Common Pitfalls and How to Avoid Them

• Delaying ART while awaiting complete laboratory results—only defer for HLA-B*5701 when planning abacavir; start treatment immediately otherwise. 1, 4

• Failing to perform HLA-B*5701 testing before prescribing abacavir—this can lead to fatal hypersensitivity reactions in approximately 50% of positive patients. 1, 4, 5

• Using rilpivirine in patients with high viral load (>100,000 copies/mL) or low CD4 (<200 cells/µL)—this results in markedly higher virologic failure rates. 1, 4

• Prescribing TDF to patients with renal disease or osteoporosis—switch to TAF instead. 2, 1, 4

• Starting abacavir or NNRTIs for same-day initiation—these require baseline testing that delays therapy; use tenofovir-based InSTI regimens instead. 1, 4

• Initiating ART too early in cryptococcal meningitis—delay 4–6 weeks after antifungal therapy to reduce IRIS risk. 1

• Prescribing MAC prophylaxis when starting ART promptly—this is unnecessary and should be omitted. 1

• Overlooking drug interactions with cobicistat-boosted regimens or rifampin—these can lead to treatment failure or adverse effects. 1, 4

• Using dolutegravir/lamivudine two-drug regimen without confirming HIV RNA <500,000 copies/mL, absence of lamivudine resistance, and no HBV co-infection—inappropriate use leads to treatment failure. 4