What are the initial testing and treatment guidelines for a patient with a new HIV diagnosis?

Initial Testing and Treatment Guidelines for New HIV Diagnosis

Immediate Action: Start ART as Soon as Possible

Antiretroviral therapy should be initiated immediately after HIV diagnosis—ideally at the first clinic visit—regardless of CD4 count or viral load. 1 This approach has been shown to reduce mortality by 74% compared to deferring treatment, and significantly decreases AIDS progression, tuberculosis, and other opportunistic infections 1, 2.

Initial Laboratory Testing (Draw Before Starting ART, But Don't Delay Treatment)

Before initiating ART, obtain the following tests, but do not wait for results to start treatment 1:

Essential Pre-Treatment Labs:

• HIV-1 RNA level (viral load) 1
• CD4+ cell count 1
• HIV genotype resistance testing (reverse transcriptase and protease) 1
• HLA-B*5701 testing (mandatory if considering abacavir-containing regimens) 1
• Hepatitis A, B, and C serology 1
• Complete blood count, comprehensive metabolic panel, liver function tests 1
• Fasting lipid profile and glucose 1
• Pregnancy test (in people of childbearing potential) 1
• Urinalysis for glucose and protein 1

Additional Testing:

• Cryptococcal antigen if CD4 count <100 cells/μL 1
• Tuberculosis screening (interferon-gamma release assay or tuberculin skin test) 1
• Sexually transmitted infection screening at all exposed mucosal sites 1
• Syphilis serology 1

Note: Integrase inhibitor resistance testing is not routinely recommended unless the patient previously took cabotegravir PrEP or acquired HIV from a partner with known InSTI resistance 1.

Recommended First-Line ART Regimens

Generally Recommended Regimens (Listed Alphabetically):

Bictegravir/tenofovir alafenamide (TAF)/emtricitabine is the preferred first-line regimen for most patients 1, 3. This single-tablet regimen has the highest evidence rating (AIa) and offers:

• High barrier to resistance
• Minimal drug interactions
• Once-daily dosing
• Excellent tolerability 1

Dolutegravir plus TAF/emtricitabine is equally recommended 1, 3. This combination provides:

• Excellent efficacy across all viral loads
• Favorable renal and bone safety profile compared to tenofovir disoproxil fumarate (TDF) 1
• Once-daily dosing 1

Dolutegravir/abacavir/lamivudine is recommended but requires negative HLA-B*5701 testing before use 1. Approximately 50% of HLA-B*5701-positive individuals will develop potentially life-threatening hypersensitivity reactions 4.

Alternative Regimens (When InSTI Not Available):

• Darunavir/cobicistat plus TAF/emtricitabine 1, 5
• Darunavir boosted with ritonavir plus TAF/emtricitabine 1, 5
• Efavirenz/TDF/emtricitabine (older option, more side effects) 1

Critical Caveat: NNRTIs (like efavirenz) and abacavir should NOT be used for rapid same-day ART initiation due to the need for HLA-B*5701 testing results and higher risk of resistance 1.

Special Considerations for ART Initiation

Opportunistic Infections:

• Most opportunistic infections: Start ART within 2 weeks of beginning OI treatment 1, 6
• Tuberculosis with CD4 ≥50 cells/μL: Start ART within 2-8 weeks of TB treatment 1, 6, 7
• Tuberculosis with CD4 <50 cells/μL: Start ART within 2 weeks of TB treatment 1, 6, 7
• Cryptococcal meningitis: Delay ART for 2-4 weeks after starting antifungal therapy to reduce IRIS risk 1, 6
• Pneumocystis pneumonia (PCP): Start ART within 2 weeks once clinically stable on PCP treatment 6

Hepatitis B Co-infection:

Patients with HBV co-infection must receive ART containing TAF or TDF plus lamivudine or emtricitabine 1. These agents treat both HIV and HBV simultaneously.

Pregnancy:

Pregnant patients should receive darunavir 600 mg with ritonavir 100 mg twice daily rather than once-daily dosing 5. However, bictegravir- or dolutegravir-based regimens are also acceptable 1.

Monitoring After ART Initiation

Early Monitoring (First 6 Months):

• Viral load at 4-6 weeks after starting ART to assess initial response 1
• Viral load every 4-6 weeks until undetectable (<20-50 copies/mL) 1
• Virologic suppression should occur within 24 weeks of ART initiation 1
• Assess adherence and tolerability at each visit 1

Long-Term Monitoring:

• Viral load every 3 months until suppressed for at least 1 year 1
• Viral load every 6 months after 1 year of sustained suppression in adherent patients 1
• CD4 count every 6 months until >250 cells/μL for at least 1 year with viral suppression 1
• After CD4 >500 cells/μL for 2 years with viral suppression, CD4 monitoring can be discontinued unless virologic failure occurs 1

Safety Monitoring:

• Renal function (estimated GFR, urinalysis) especially with tenofovir-containing regimens 1
• Liver function tests especially in patients with hepatitis co-infection or baseline elevations 1, 5
• Fasting lipids and glucose 1
• Bone density screening in patients at risk for osteoporosis, particularly if using TDF 1

Opportunistic Infection Prophylaxis

Pneumocystis Pneumonia (PCP):

Primary prophylaxis with trimethoprim-sulfamethoxazole is mandatory for CD4 <200 cells/μL 1, 6. Continue prophylaxis even after starting ART until CD4 rises above 200 cells/μL for at least 3 months 6.

Mycobacterium Avium Complex (MAC):

Primary MAC prophylaxis is no longer recommended if effective ART is initiated immediately 1, 6. The incidence of MAC with early ART is sufficiently low that prophylaxis is unnecessary.

Cryptococcal Disease:

Primary prophylaxis is not recommended in high-resource settings with low disease prevalence 1.

Common Pitfalls and How to Avoid Them

Critical Errors to Avoid:

1. Delaying ART while waiting for lab results: Start treatment immediately; adjust later if resistance testing indicates changes are needed 1. Delaying ART increases mortality risk 8, 2.

2. Not testing for HLA-B*5701 before prescribing abacavir: This can cause potentially fatal hypersensitivity reactions in 50% of positive individuals 1, 4. The test must be completed before starting abacavir.

3. Using NNRTIs or abacavir for same-day ART initiation: These should be avoided for rapid start due to resistance concerns and need for HLA testing 1.

4. Starting ART too early in cryptococcal meningitis: Unlike other OIs, ART should be delayed 2-4 weeks in cryptococcal meningitis to reduce IRIS risk 1, 6. This is a critical exception to the "start within 2 weeks" rule.

5. Confusing TDF with TAF: TDF is not recommended for patients with or at risk for kidney disease or osteoporosis 1. TAF has superior renal and bone safety profiles.

6. Overlooking drug interactions: Boosted regimens (with ritonavir or cobicistat) have extensive drug interactions that must be reviewed 5. Unboosted InSTI regimens are preferred to minimize interactions 1.

7. Assuming high CD4 counts mean treatment can wait: Even patients with CD4 >500 cells/μL benefit from immediate ART initiation, though they may have higher attrition rates requiring enhanced adherence support 1, 8, 9.

Structural Barriers:

Remove all barriers to same-day ART initiation including insurance authorization delays, pharmacy access issues, and appointment scheduling constraints 1. Studies show that rapid ART programs reduce time to viral suppression by more than 50% 1.