What is the next step in managing a 25-year-old male PLHIV with a low CD4 count, presenting with fever, diplopia, and headache?

Management of Fever, Diplopia, and Headache in a 25-Year-Old Male with HIV and Low CD4 Count

The next step in managing this patient should be an urgent lumbar puncture with CSF analysis to rule out cryptococcal meningitis, which is the most likely diagnosis given the clinical presentation.

Clinical Assessment

This 25-year-old male with HIV presents with a concerning clinical triad:

• Fever
• Double vision (diplopia)
• Headache
• Low CD4 count (9%)

This presentation in an HIV-positive patient with severe immunosuppression (CD4 count <10%) strongly suggests central nervous system (CNS) infection, particularly cryptococcal meningitis.

Diagnostic Approach

Immediate Steps:

1. Lumbar puncture with comprehensive CSF analysis:

   • Opening pressure measurement (critical for cryptococcal meningitis)
   • Cell count and differential
   • Protein and glucose levels
   • India ink stain
   • Cryptococcal antigen testing
   • Fungal culture
   • PCR for other pathogens (TB, toxoplasmosis)

2. Serum cryptococcal antigen testing (can be performed while preparing for LP)

3. Brain imaging:

   • MRI with contrast is preferred over CT to evaluate for:
     • Mass lesions (toxoplasmosis, lymphoma)
     • Meningeal enhancement
     • Cryptococcomas
     • Other CNS pathologies

Additional Testing:

• Complete blood count
• Comprehensive metabolic panel
• Blood cultures
• Serum toxoplasma IgG
• TB testing (interferon-gamma release assay)
• CD4 count and HIV viral load (if not recently done)

Likely Diagnosis and Management

Cryptococcal Meningitis

Based on the clinical presentation in a severely immunocompromised patient, cryptococcal meningitis is the most likely diagnosis 1. Management should include:

1. Induction therapy (2 weeks):

   • Liposomal amphotericin B (3-4 mg/kg/day IV) plus flucytosine (100 mg/kg/day orally in 4 divided doses) 1

2. Consolidation therapy (8 weeks):

   • Fluconazole 400-800 mg daily 1

3. Maintenance therapy:

   • Fluconazole 200 mg daily until immune reconstitution 1, 2

4. Management of increased intracranial pressure:

   • If opening pressure >25 cm H₂O, remove CSF to reduce pressure by 50% or to normal levels 1
   • Daily lumbar punctures may be required until pressure normalizes
   • Consider acetazolamide if increased ICP persists 2

Alternative Diagnoses to Consider

1. Toxoplasmosis:

   • More likely to present with focal neurological deficits
   • Treatment: Pyrimethamine plus sulfadiazine plus leucovorin 1

2. Tuberculous meningitis:

   • Consider especially with history of TB exposure
   • Treatment: Standard anti-TB regimen plus steroids 3

3. Viral meningoencephalitis (including EBV):

   • Can present with similar symptoms 4
   • Supportive care and antiretrovirals

4. Primary CNS lymphoma:

   • More likely with focal deficits and contrast-enhancing lesions on MRI
   • Requires brain biopsy for definitive diagnosis

Antiretroviral Therapy Considerations

• Do not start ART immediately if cryptococcal meningitis is confirmed
• Delay ART initiation by 4-6 weeks after antifungal therapy to reduce risk of immune reconstitution inflammatory syndrome (IRIS) 1
• If already on ART, continue current regimen

Supportive Care

• Ensure adequate hydration
• Antipyretics for fever
• Analgesics for headache
• Monitor neurological status closely
• Consider ICU admission if altered mental status develops

Prognosis and Follow-up

• Cryptococcal meningitis carries significant mortality (13.3% in some studies) even with appropriate treatment 3
• Regular follow-up lumbar punctures to ensure sterilization of CSF
• Monitor for drug toxicities (renal function with amphotericin B, bone marrow suppression with flucytosine)
• Long-term follow-up to monitor for relapse

Prevention of Other Opportunistic Infections

• Initiate PJP prophylaxis (trimethoprim-sulfamethoxazole) 1
• Consider MAC prophylaxis (azithromycin) given very low CD4 count
• Evaluate for other opportunistic infections

The patient's extremely low CD4 count (9%) puts him at high risk for multiple opportunistic infections, but the clinical presentation with fever, headache, and diplopia strongly suggests cryptococcal meningitis as the most likely diagnosis requiring urgent evaluation and treatment.