In an HIV‑positive patient with a CD4+ T‑lymphocyte count of 9 cells/µL, which prophylactic regimens should be initiated?

Prophylaxis for HIV Patient with CD4 Count of 9 cells/µL

An HIV-positive patient with a CD4 count of 9 cells/µL requires immediate initiation of trimethoprim-sulfamethoxazole (TMP-SMZ) double-strength daily for PCP and toxoplasmosis prophylaxis, plus azithromycin 1200 mg weekly for MAC prophylaxis, alongside immediate antiretroviral therapy (ART) initiation. 1, 2

Core Prophylactic Regimens

Pneumocystis jirovecii Pneumonia (PCP) - MANDATORY

• TMP-SMZ double-strength (800/160 mg) once daily is the preferred regimen for all patients with CD4 <200 cells/µL 3, 2
• This single agent simultaneously provides protection against toxoplasmosis in seropositive patients 3
• Alternative regimens if TMP-SMZ intolerant: 3, 2
  • Dapsone 100 mg daily (PCP only), OR
  • Dapsone 50 mg daily + pyrimethamine 50 mg weekly + leucovorin 25 mg weekly (covers both PCP and toxoplasmosis), OR
  • Atovaquone 1500 mg daily
• Critical pitfall: Aerosolized pentamidine does NOT protect against toxoplasmosis and should be avoided in patients at this CD4 level 3, 2

Toxoplasmosis - MANDATORY if Seropositive

• At CD4 <100 cells/µL, toxoplasmosis prophylaxis is essential for seropositive patients 3
• TMP-SMZ double-strength daily already provides adequate coverage - no additional agent needed 3
• If toxoplasma serology unknown: Check IgG antibody status immediately; if positive, the TMP-SMZ regimen suffices 3
• If seronegative, retest when CD4 was <100 cells/µL to detect seroconversion 3

Mycobacterium avium Complex (MAC) - MANDATORY

• Azithromycin 1200 mg once weekly is the preferred prophylaxis for CD4 <50 cells/µL 1, 2
• Clarithromycin 500 mg twice daily is equally effective but has more drug interactions with ART 1
• Rifabutin 300 mg daily is an alternative but requires careful dose adjustments with protease inhibitors 1
• Do NOT combine clarithromycin + rifabutin - increases toxicity without improving efficacy 1
• Critical step: Rule out active disseminated MAC disease clinically before starting prophylaxis 1

Antiretroviral Therapy - IMMEDIATE INITIATION

Timing and Approach

• Start ART immediately (same-day or within days) regardless of prophylaxis status 1
• Draw baseline labs (HIV RNA, CD4, genotype, hepatitis panel) but do NOT delay ART for results 1
• Preferred first-line regimens: 1
  • Bictegravir/tenofovir alafenamide/emtricitabine, OR
  • Dolutegravir + tenofovir/emtricitabine
• Avoid NNRTIs and abacavir before genotype results are available 1

Drug Interaction Management

• Azithromycin has fewer interactions than clarithromycin with protease inhibitors - this is why it's preferred 1
• Rifabutin requires dose adjustments with most protease inhibitors 1
• TMP-SMZ has minimal ART interactions 3, 2
• Coordinate with HIV specialist to optimize regimen compatibility 3

Additional Prophylaxis Considerations

Herpes Viruses

• Acyclovir or valacyclovir prophylaxis is strongly recommended if history of HSV or VZV infection 3
• Consider prophylaxis even without prior history given severe immunosuppression 3

Cytomegalovirus (CMV)

• Monitor for CMV disease when CD4 <100 cells/µL 3
• No routine primary prophylaxis recommended, but maintain high clinical suspicion 3
• Screen for CMV retinitis with dilated fundoscopic exam 3

Fungal Infections

• Fluconazole prophylaxis may be considered at CD4 <100 cells/µL for patients with recurrent candidiasis or anticipated prolonged neutropenia 3
• Routine primary prophylaxis for invasive fungal disease is NOT recommended 3

Bacterial Infections

• TMP-SMZ provides cross-protection against many bacterial respiratory infections 3, 2
• Consider fluoroquinolone prophylaxis if intensive chemotherapy or prolonged neutropenia expected 3

Tuberculosis Screening - ESSENTIAL

• Rule out active TB before starting any prophylaxis - especially critical before rifabutin 1
• Perform tuberculin skin test or interferon-gamma release assay 4
• If latent TB infection confirmed and active TB excluded: isoniazid 300 mg daily for 9-12 months 4, 5

Practical Implementation Algorithm

Step 1: Immediate same-day interventions

• Start TMP-SMZ double-strength daily
• Start azithromycin 1200 mg weekly
• Initiate ART (integrase inhibitor-based regimen)
• Draw baseline labs (don't wait for results)

Step 2: Within 24-48 hours

• Check toxoplasma IgG serology
• Screen for active TB (chest X-ray, symptom review)
• Assess for active MAC disease (blood cultures if febrile)
• Dilated fundoscopic exam for CMV retinitis

Step 3: Ongoing management

• Monitor for immune reconstitution inflammatory syndrome (IRIS) 1
• Check CD4 and viral load at 4 weeks, then every 3 months
• Continue prophylaxis until CD4 >200 cells/µL for ≥3 months on ART 2, 6

Common Pitfalls to Avoid

• Never use aerosolized pentamidine alone at this CD4 level - it misses toxoplasmosis entirely 3, 2
• Don't delay ART waiting for genotype results - start immediately with integrase inhibitor regimen 1
• Don't forget TB screening - starting rifabutin without excluding active TB risks resistance 1
• Don't combine clarithromycin + rifabutin for MAC prophylaxis 1
• Don't stop prophylaxis prematurely - requires CD4 >200 cells/µL sustained for ≥3 months, not just viral suppression 2, 6

When to Discontinue Prophylaxis

Infection	CD4 Threshold	Duration Above Threshold	Additional Criteria
PCP	>200 cells/µL	≥3 months	On effective ART [2]
Toxoplasmosis	>200 cells/µL	≥3 months	On effective ART [2]
MAC	>100 cells/µL	≥3 months	On effective ART [1]

Critical note: Base discontinuation decisions on the sustained CD4 rise, not merely on undetectable viral load 2, 6