What prophylactic antibiotics and dosing should be given to an HIV‑infected adult based on CD4 count thresholds?

Prophylactic Antibiotics for HIV-Infected Adults Based on CD4 Count

All HIV-infected adults with CD4 counts <200 cells/µL should receive trimethoprim-sulfamethoxazole (TMP-SMX) one double-strength tablet (800/160 mg) daily as first-line prophylaxis against Pneumocystis jirovecii pneumonia (PCP), which simultaneously provides protection against toxoplasmosis in seropositive patients. 1, 2

CD4-Based Prophylaxis Algorithm

CD4 <200 cells/µL: PCP Prophylaxis (Mandatory)

• Primary regimen: TMP-SMX double-strength (DS) tablet once daily 1

  • This single agent provides dual coverage against both PCP and toxoplasmosis in Toxoplasma-IgG positive patients 1, 2
  • Additional benefit: reduces bacterial respiratory infections 1

• Alternative regimens if TMP-SMX intolerant:

  • Dapsone 100 mg daily (PCP only—does NOT cover toxoplasmosis) 1
  • Atovaquone 1500 mg daily (PCP only) 1, 3
  • Aerosolized pentamidine 300 mg monthly via Respirgard II nebulizer (least preferred—no toxoplasmosis coverage) 1, 4

• Additional indications for PCP prophylaxis regardless of CD4:

  • History of oropharyngeal candidiasis (thrush) 1, 4
  • Prior episode of PCP 1
  • Unexplained fever >100°F for ≥2 weeks 5

CD4 <100 cells/µL: Add Toxoplasmosis Prophylaxis (If Seropositive)

• If Toxoplasma-IgG positive AND already on TMP-SMX DS daily: no additional agent needed 1, 2

  • TMP-SMX DS daily alone provides adequate toxoplasmosis prophylaxis 1, 2

• If Toxoplasma-IgG positive but TMP-SMX intolerant:

  • Dapsone 50 mg daily PLUS pyrimethamine 50 mg weekly PLUS leucovorin 25 mg weekly 1, 2

• If Toxoplasma serology unknown: obtain IgG testing immediately 2

  • If negative, repeat testing when CD4 remains <100 cells/µL to detect seroconversion 2

CD4 <50 cells/µL: Add MAC Prophylaxis

• Primary regimen: Azithromycin 1200 mg once weekly (preferred) 1, 2

  • Better adherence due to weekly dosing 2
  • Fewer drug interactions than clarithromycin 2
  • Provides additional protection against bacterial respiratory infections 1

• Alternative: Clarithromycin 500 mg twice daily 1, 2

  • Equally effective but more drug interactions with protease inhibitors 1, 2

• Second-line: Rifabutin 300 mg daily 1, 2

  • Requires dose adjustments with most antiretroviral agents 1, 2
  • Must exclude active tuberculosis before starting 2

• Important caveat: With immediate ART initiation and rapid viral suppression, some experts no longer routinely prescribe MAC prophylaxis, though many clinicians still do 1, 2

Discontinuation Criteria (When to Stop Prophylaxis)

Stopping PCP Prophylaxis

• CD4 >200 cells/µL sustained for >3 months on ART 1, 2
• Must have undetectable or suppressed viral load 6

Stopping Toxoplasmosis Prophylaxis

• CD4 >200 cells/µL sustained for >3 months on ART 1, 2
• Patient must be asymptomatic for toxoplasmosis 1

Stopping MAC Prophylaxis

• CD4 >100 cells/µL sustained for >3 months on ART 1, 2
• Some guidelines use >50 cells/µL threshold 2

Restarting Prophylaxis

• Restart if CD4 falls below the original threshold 1, 2
  • PCP/toxoplasmosis: restart if CD4 <200 cells/µL 1
  • MAC: restart if CD4 <50-100 cells/µL 1

Critical Drug Interactions and Safety Considerations

G6PD Deficiency

• Dapsone is absolutely contraindicated in G6PD deficiency due to hemolysis risk 3
• Primaquine is also contraindicated 3
• Use atovaquone 1500 mg daily as the safest alternative 3

Rifabutin Interactions

• Requires dose adjustments with protease inhibitors and NNRTIs 1, 2
• Consult specialist for specific dosing 1
• Must exclude active TB before starting to avoid inducing resistance 2

Clarithromycin Interactions

• Significant interactions with protease inhibitors 1, 2
• Azithromycin preferred due to fewer interactions 2

TMP-SMX Compatibility

• Minimal interactions with modern ART regimens 2
• Compatible with integrase inhibitors, protease inhibitors, and NNRTIs 2

Antiretroviral Therapy Timing

• Start ART immediately upon HIV diagnosis, even before genotype results 1, 2

• Preferred first-line regimens:

  • Bictegravir/tenofovir alafenamide/emtricitabine 1, 2
  • Dolutegravir + tenofovir + emtricitabine 1, 2

• For active opportunistic infections:

  • Start ART within 2 weeks for most OIs 1, 5
  • For TB with CD4 <50 cells/µL: start ART within 2 weeks of TB treatment 1, 5
  • For TB with CD4 ≥50 cells/µL: start ART within 2-8 weeks 1, 5

Common Pitfalls to Avoid

• Never use aerosolized pentamidine as first-line when TMP-SMX is tolerated—it lacks systemic coverage and does not prevent toxoplasmosis 1, 2

• Never combine clarithromycin + rifabutin for MAC prophylaxis—increases adverse effects without improving efficacy 1, 2

• Never prescribe dapsone or primaquine without checking G6PD status first—can cause life-threatening hemolysis 3

• Never delay PCP prophylaxis while waiting for CD4 results if patient has thrush or prior AIDS-defining illness 1, 5

• Never stop prophylaxis based on a single CD4 measurement—require sustained elevation >3 months 1, 2

• Never use TMP-SMX indiscriminately when not indicated for prophylaxis—promotes drug-resistant organisms 1

• Never forget to check Toxoplasma serology when CD4 <100 cells/µL—determines need for specific prophylaxis 2

• Never assume MAC prophylaxis is unnecessary in patients with CD4 <50 cells/µL, even on ART—many experts still recommend it 2