What is the recommended treatment for a patient with active HIV Ag/Ab (Antibody/Antigen) 4th generation results and leukocytosis (increased white blood cell count)?

Treatment for HIV with Positive Ag/Ab 4th Generation Results and Leukocytosis

For patients with positive HIV Ag/Ab 4th generation test results and leukocytosis, immediate initiation of antiretroviral therapy (ART) with a regimen of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) or dolutegravir plus tenofovir/emtricitabine (DTG plus TXF/FTC) is strongly recommended regardless of CD4 cell count. 1, 2

Diagnostic Confirmation

Before initiating treatment:

1. Confirm HIV diagnosis with:

   • HIV RNA viral load testing
   • CD4 cell count
   • HIV genotype testing for NRTI, NNRTI, and PI resistance 2

2. Evaluate leukocytosis:

   • Complete blood count with differential
   • Assess for concurrent infections or inflammatory conditions
   • Consider bone marrow evaluation if leukocytosis is severe or unexplained

Recommended First-Line Regimens

The 2024 International Antiviral Society-USA panel recommends the following regimens (in alphabetical order by anchor drug) for most people with HIV 1:

• BIC/TAF/FTC (evidence rating: AIa)
• Dolutegravir plus TXF/XTC (evidence rating: AIa)
• DTG/3TC (only if HIV RNA <500,000 copies/mL, no lamivudine resistance, and no HBV co-infection) (evidence rating: AIa)

Special Considerations for Leukocytosis

Leukocytosis in HIV-positive patients may be due to:

1. Acute HIV infection (seroconversion illness)
2. Opportunistic infections
3. Malignancies associated with HIV
4. Medication effects

For patients with leukocytosis:

• Investigate underlying causes while initiating ART
• Consider opportunistic infection workup based on clinical presentation
• Monitor white blood cell count after initiating ART

Timing of ART Initiation

ART should be initiated immediately upon diagnosis, with special considerations for opportunistic infections 1, 2:

• For patients with active tuberculosis without meningitis: Start ART within 2 weeks of TB treatment, especially if CD4 count <50/μL
• For tuberculous meningitis: Start TB treatment and corticosteroids immediately, then ART within 2-4 weeks
• For cryptococcal meningitis: Start ART 2-4 weeks after antifungal therapy
• For newly diagnosed cancer: Start ART immediately with attention to drug interactions

Monitoring After Treatment Initiation

After starting ART, regular monitoring should include:

1. HIV viral load at 4-8 weeks, then every 3 months
2. CD4 cell count every 3-6 months
3. Complete blood count to monitor leukocytosis
4. Liver and kidney function tests
5. Assessment for immune reconstitution inflammatory syndrome (IRIS)

Potential Challenges

1. Delayed immune recovery: Patients presenting with advanced disease may have blunted CD4 recovery despite viral suppression 3

2. Medication adherence: Ensure patient understands importance of consistent medication adherence to prevent resistance development 4

3. Drug resistance: For patients who acquired HIV while on PrEP, genotype testing is crucial before starting therapy 1

4. IRIS: Monitor for worsening symptoms after ART initiation, particularly in patients with low CD4 counts and opportunistic infections

Prognosis

Early initiation of ART has been shown to improve long-term outcomes, even in patients presenting with low CD4 counts 3, 5. While late presenters may have more clinical events in the first year of treatment, by year two their outcomes can approach those of patients who started treatment earlier 3.

The leukocytosis should be monitored and is expected to improve with effective HIV treatment, particularly if it is related to the HIV infection itself rather than a separate pathological process.