What is the initial approach to a 39-year-old patient with a new diagnosis of Human Immunodeficiency Virus (HIV)?

Initial Approach to a 39-Year-Old Patient with Newly Diagnosed HIV

Start antiretroviral therapy (ART) immediately at the first clinic visit—ideally the same day as diagnosis—if the patient is ready to commit to treatment. 1, 2

Immediate Actions at First Visit

Confirm Diagnosis and Assess Readiness

• Verify positive HIV test result and confirm the patient understands the diagnosis 2
• Assess patient's readiness to commit to lifelong treatment; if ready, proceed with same-day ART initiation 1, 2
• Do not delay treatment for "counseling sessions" or multiple pre-treatment visits—these structural barriers must be removed 1, 2

Draw Baseline Laboratory Tests (But Do Not Wait for Results)

Critical principle: Draw labs immediately but start ART before results return 1, 2

Required baseline tests include:

• HIV-1 RNA viral load 1, 2
• CD4 cell count 1, 2
• HIV genotype for resistance testing (NRTI, NNRTI, PI, and integrase inhibitors) 1, 2
• Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody 1, 2
• Complete metabolic panel (renal and hepatic function) 1, 2
• Complete blood count 1
• Fasting lipid panel and glucose 1
• Pregnancy test (if applicable) 1
• HLA-B*5701 testing ONLY if considering abacavir—this is the ONE test you must wait for 1, 2

Screen for Opportunistic Infections

Assess for symptoms of:

• Tuberculosis: cough, fever, night sweats, weight loss 1, 3
• Pneumocystis pneumonia (PCP): dyspnea, dry cough, fever 3
• Cryptococcal meningitis: headache, altered mental status, fever 4
• Toxoplasmosis: focal neurologic deficits, seizures, confusion 1
• Candidiasis: oral thrush, dysphagia 1

If CD4 count is available and <200 cells/μL, initiate trimethoprim-sulfamethoxazole prophylaxis immediately for PCP prevention 1, 3

Select and Initiate ART Regimen

Preferred Regimens for Same-Day Start

Use integrase strand transfer inhibitor (InSTI)-based regimens for rapid initiation 1, 2, 5

First-line options (in alphabetical order):

• Bictegravir/tenofovir alafenamide (TAF)/emtricitabine (single tablet, once daily) 1, 2
• Dolutegravir plus TAF/emtricitabine (two tablets, once daily) 1, 2
• Raltegravir plus TAF/emtricitabine (multiple tablets, twice daily for raltegravir) 1, 2

Regimens to AVOID for Rapid Start

Do not use these regimens for same-day initiation 1, 2:

• Dolutegravir/abacavir/lamivudine: requires HLA-B*5701 testing first 1, 2
• Any NNRTI-based regimen (efavirenz, rilpivirine): requires baseline viral load and resistance testing results 1, 2
• Abacavir-containing regimens: risk of hypersensitivity reaction without HLA-B*5701 testing 1, 2

Rationale for InSTI-Based Regimens

InSTI-based regimens are preferred because they provide:

• Rapid viral suppression (median 1.8 months vs. 4.3 months with delayed start) 6
• High barrier to resistance 5
• Minimal drug-drug interactions 3
• Excellent tolerability 1, 5
• Once-daily dosing options 1

Special Circumstances Requiring Modified Timing

If Opportunistic Infection is Present

For most opportunistic infections: Start ART within 2 weeks of OI treatment initiation 1, 3

For tuberculosis:

• CD4 <50 cells/μL: Start ART within 2 weeks of TB treatment 1
• CD4 ≥50 cells/μL: Start ART within 2-8 weeks of TB treatment 1
• Use dolutegravir 50 mg twice daily (not once daily) with rifampin 1

For cryptococcal meningitis: This is the major exception—delay ART for 4-6 weeks after starting antifungal therapy 1, 4

• May consider 2-week initiation only if patient has clinically improved, controlled intracranial pressure, negative CSF cultures, and can be closely monitored 4
• Earlier initiation increases mortality risk due to immune reconstitution inflammatory syndrome (IRIS) 4

For PCP: Start ART within 2 weeks once patient is clinically stable on PCP treatment and corticosteroids 3

For malignancy: Start ART immediately with attention to drug-drug interactions 1

Follow-Up and Monitoring

First Follow-Up Visit (2-4 Weeks)

• Review baseline laboratory results and adjust regimen if needed based on resistance testing 1, 2
• Assess medication adherence and side effects 5
• Check HIV viral load to document early response 5, 6
• Reinforce importance of adherence 5

Subsequent Monitoring

• HIV viral load at 4-8 weeks, then every 3-6 months once suppressed 1
• CD4 count every 3-6 months until >200 cells/μL on ART for >1 year 1
• Monitor for IRIS in first 2-3 months, especially if baseline CD4 <100 cells/μL 3, 4
• Assess for medication toxicities (renal function, bone density, metabolic parameters) 1

Common Pitfalls to Avoid

Pitfall #1: Delaying ART while waiting for complete laboratory results

• Only HLA-B*5701 requires waiting (and only if using abacavir) 1, 2
• Resistance testing results can guide adjustments later if needed 1, 2
• Delaying treatment increases mortality, morbidity, and transmission risk 1, 7

Pitfall #2: Using abacavir or NNRTIs for same-day start

• These regimens require baseline testing that takes days to weeks 1, 2
• Use InSTI-based regimens instead 1, 2

Pitfall #3: Starting ART too early in cryptococcal meningitis

• Unlike other OIs, early ART in cryptococcal meningitis increases mortality 1, 4
• Wait 4-6 weeks unless strict clinical criteria are met 4

Pitfall #4: Forgetting PCP prophylaxis

• If CD4 <200 cells/μL, start trimethoprim-sulfamethoxazole immediately 1, 3
• Continue prophylaxis even after starting ART until CD4 >200 cells/μL for >3 months 3

Pitfall #5: Assuming MAC prophylaxis is needed

• MAC prophylaxis is no longer recommended if effective ART is initiated immediately 1, 3

Evidence Supporting Rapid Initiation

The recommendation for same-day ART initiation is supported by:

• Randomized controlled trials showing 36% increase in ART uptake and 26% increase in viral suppression with rapid initiation 8
• Observational studies demonstrating faster time to viral suppression (1.8 vs. 4.3 months) without increased toxicity or loss to follow-up 6
• Biological rationale: 1-10 billion viruses replicate daily, driving inflammation and immune damage that increases risk of cardiovascular disease, malignancy, and other comorbidities 7
• Public health benefit: Treatment is prevention—suppressed patients cannot transmit HIV 7

The 2020 International Antiviral Society-USA guidelines provide the highest level of evidence (AIa rating) for immediate ART initiation 1, representing a paradigm shift from earlier approaches that delayed treatment 9. With modern regimens that are highly effective and well-tolerated, there is no benefit to waiting and significant harm in delaying therapy 7.