What prophylaxis is recommended for a patient with a severely impaired immune system, indicated by a CD4 (Cluster of Differentiation 4) count less than 18, to prevent opportunistic infections?

Prophylaxis for CD4 Count Less Than 18 cells/µL

A patient with a CD4 count less than 18 cells/µL requires immediate initiation of multiple prophylactic regimens: TMP-SMX (trimethoprim-sulfamethoxazole) one double-strength tablet daily for PCP and toxoplasmosis, plus azithromycin 1200 mg weekly (or clarithromycin 500 mg twice daily) for disseminated MAC disease. 1, 2

Primary Prophylaxis Against PCP and Toxoplasmosis

TMP-SMX is the first-line agent for patients with CD4 counts below 200 cells/µL, and this patient with a CD4 count of less than 18 cells/µL is at extremely high risk. 1, 2

Dosing Regimen

• Preferred regimen: TMP-SMX one double-strength tablet (800 mg sulfamethoxazole/160 mg trimethoprim) daily 2
• Alternative dosing: One single-strength tablet daily is also effective and may be better tolerated 1
• Three times weekly dosing: One double-strength tablet three times per week is acceptable but less protective 1

Dual Protection Benefit

• TMP-SMX provides cross-protection against toxoplasmosis, which is critical at this CD4 level (below 100 cells/µL where toxoplasmosis prophylaxis is indicated) 1, 2
• Additional protection against common respiratory bacterial infections is conferred by TMP-SMX 1, 2

Alternative Regimens if TMP-SMX Cannot Be Tolerated

If the patient experiences non-life-threatening adverse reactions to TMP-SMX, attempt to continue the medication if clinically feasible or consider gradual reintroduction with dose escalation (desensitization). 1, 2

If TMP-SMX must be discontinued, alternative regimens include:

• Dapsone 100 mg orally once daily (provides PCP protection only) 1, 2
• Dapsone 50 mg daily PLUS pyrimethamine 50 mg weekly PLUS leucovorin 25 mg weekly (provides protection against both PCP and toxoplasmosis) 1, 2
• Atovaquone 1500 mg orally once daily (effective alternative, safe in G6PD deficiency) 1, 3, 4
• Aerosolized pentamidine 300 mg monthly via Respirgard II nebulizer (less effective, no toxoplasmosis protection) 1

Critical caveat: Check for G6PD deficiency before prescribing dapsone, as it is absolutely contraindicated in G6PD-deficient patients due to hemolytic risk. 3

Prophylaxis Against Disseminated MAC Disease

At CD4 counts below 50 cells/µL, prophylaxis against disseminated Mycobacterium avium complex (MAC) is mandatory. 1

Recommended Regimens

• Azithromycin 1200 mg orally once weekly (preferred due to convenience and fewer drug interactions) 1
• Clarithromycin 500 mg orally twice daily (alternative option) 1
• Rifabutin 300 mg orally once daily (less preferred due to significant drug interactions with protease inhibitors and NNRTIs; requires specialist consultation) 1

Important consideration: Rifabutin has substantial drug interactions with antiretroviral therapy and should only be used after consultation with a specialist. 1

Additional Prophylactic Considerations at This CD4 Level

Cryptococcosis and Other Fungal Infections

• No routine primary prophylaxis is recommended for cryptococcosis, histoplasmosis, or coccidioidomycosis in the absence of prior disease 1
• Secondary prophylaxis is required only after documented disease 1

CMV Retinitis

• No primary prophylaxis is recommended for CMV retinitis 1
• Regular ophthalmologic examinations should be considered at this CD4 level to detect early disease

Bacterial Infections

• TMP-SMX provides additional protection against common bacterial respiratory pathogens 2
• Consider IVIG only if recurrent bacterial infections occur despite TMP-SMX prophylaxis 1

Duration and Discontinuation Criteria

Prophylaxis should be continued indefinitely until immune reconstitution occurs with antiretroviral therapy. 2

Criteria for Discontinuing Primary Prophylaxis (Once Initiated on ART)

• PCP prophylaxis: Can be discontinued if CD4 count rises above 200 cells/µL for at least 3-6 months with sustained viral suppression 1, 5
• Toxoplasmosis prophylaxis: Can be discontinued if CD4 count rises above 200 cells/µL for at least 3 months 1
• MAC prophylaxis: Can be discontinued if CD4 count rises above 100 cells/µL for at least 3 months 1

Criteria for Restarting Prophylaxis

• Restart PCP prophylaxis if CD4 count drops below 200 cells/µL 1
• Restart toxoplasmosis prophylaxis if CD4 count drops below 100-200 cells/µL 1
• Restart MAC prophylaxis if CD4 count drops below 50-100 cells/µL 1

Monitoring Requirements

• Check CD4 counts at least every 3 months to guide prophylaxis decisions 2
• Monitor for adverse reactions to TMP-SMX including rash, fever, cytopenias, and transaminase elevations 2
• Assess adherence to both prophylactic regimens and antiretroviral therapy regularly

Common Pitfalls to Avoid

• Do not delay prophylaxis initiation while awaiting antiretroviral therapy optimization—start immediately 1, 2
• Do not use single-agent prophylaxis when dual protection (PCP + toxoplasmosis) is needed; ensure the regimen covers both pathogens 1
• Do not prescribe dapsone or primaquine without first checking G6PD status 3
• Do not discontinue prophylaxis prematurely based on a single elevated CD4 count; require sustained elevation for 3-6 months 1, 5