Which opportunistic infections and corresponding prophylaxis are indicated at specific CD4+ T‑lymphocyte count thresholds in a patient with HIV?

Opportunistic Infection Prophylaxis Based on CD4+ Count in HIV/AIDS

Initiate prophylaxis at specific CD4+ thresholds: PCP and toxoplasmosis prophylaxis at CD4+ <200 cells/µL and <100 cells/µL respectively, using TMP-SMZ as the preferred agent for both.

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Primary Prophylaxis Initiation Thresholds

Pneumocystis jirovecii Pneumonia (PCP)

• Start prophylaxis when CD4+ count falls below 200 cells/µL 1
• Alternative indications include CD4+ percentage <14% or history of oropharyngeal candidiasis, even if CD4+ count is >200 cells/µL 1
• If CD4+ monitoring every 3 months is not feasible, consider initiating prophylaxis at CD4+ counts between 200-250 cells/µL to avoid missing the threshold 1

Preferred regimen: TMP-SMZ one double-strength tablet daily (most effective) 1, 2

• Alternative dosing: one single-strength tablet daily or one double-strength tablet three times weekly 1
• This regimen provides cross-protection against toxoplasmosis and common respiratory bacterial infections 1

Alternative regimens if TMP-SMZ intolerant:

• Dapsone 1
• Dapsone plus pyrimethamine plus leucovorin (also protects against toxoplasmosis) 1
• Aerosolized pentamidine via Respirgard II™ nebulizer 1
• Atovaquone 1

Toxoplasmic Encephalitis

• Start prophylaxis when CD4+ count falls below 100 cells/µL in Toxoplasma-seropositive patients 1, 3
• All HIV patients should be tested for IgG antibody to Toxoplasma immediately after HIV diagnosis 1, 3
• Seronegative patients not receiving active prophylaxis should be retested when CD4+ drops below 100 cells/µL to detect seroconversion 1, 3

Preferred regimen: TMP-SMZ one double-strength tablet daily (same as PCP prophylaxis, providing dual protection) 1, 3

Alternative regimens:

• Dapsone-pyrimethamine plus leucovorin 1, 3
• Atovaquone with or without pyrimethamine 1, 3
• Avoid: Aerosolized pentamidine does NOT protect against toxoplasmosis 1

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Discontinuing Primary Prophylaxis (HAART Era)

PCP Prophylaxis Discontinuation

• Discontinue when CD4+ count increases to >200 cells/µL for ≥3 months on HAART 1
• Most supporting studies showed median CD4+ counts >300 cells/µL at discontinuation with sustained viral suppression 1
• This reduces pill burden, drug toxicity, drug interactions, and cost without significantly increasing infection risk 1

Toxoplasmosis Prophylaxis Discontinuation

• Discontinue when CD4+ count increases to >200 cells/µL for ≥3 months on HAART 1, 3
• Supporting data from multiple observational studies and randomized trials with median follow-up of 12-22 months 1

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Restarting Primary Prophylaxis

PCP

• Restart prophylaxis if CD4+ count decreases to <200 cells/µL 1
• If initial PCP episode occurred at CD4+ >200 cells/µL, continue prophylaxis lifelong regardless of immune reconstitution 1

Toxoplasmosis

• Restart prophylaxis if CD4+ count decreases to <100-200 cells/µL 1, 3

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Secondary Prophylaxis (After Active Infection)

PCP Secondary Prophylaxis

• Patients with prior PCP require lifelong secondary prophylaxis unless immune reconstitution occurs 1
• Discontinue secondary prophylaxis when CD4+ increases from <200 to >200 cells/µL for ≥3 months on HAART 1
• Median CD4+ at discontinuation in studies was >300 cells/µL with sustained viral suppression 1

Toxoplasmosis Secondary Prophylaxis

• Preferred regimen: Pyrimethamine plus sulfadiazine plus leucovorin (highly effective and provides PCP protection) 1
• Alternative: Pyrimethamine plus clindamycin (for sulfa-intolerant patients, but does NOT protect against PCP) 1
• Discontinue when CD4+ >200 cells/µL for ≥6 months on HAART, patient remains asymptomatic, and initial therapy was successfully completed 1

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Special Populations

Pregnant Women

• Administer PCP and toxoplasmosis prophylaxis as in other adults 1
• TMP-SMZ is preferred; dapsone is an alternative 1
• Caveat: Providers may withhold prophylaxis during first trimester due to theoretical teratogenicity concerns; if withheld, consider aerosolized pentamidine for PCP (lacks systemic absorption) but note this does NOT protect against toxoplasmosis 1

Children

• Infants born to HIV-infected mothers should start TMP-SMZ prophylaxis at 4-6 weeks of age 1
• Continue through first year of life, then determine need based on age-specific CD4+ thresholds 1
• Safety of discontinuing prophylaxis in children on HAART has not been extensively studied 1

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Critical Clinical Pitfalls

Common mistake: Using aerosolized pentamidine in patients at risk for toxoplasmosis—this provides NO protection against toxoplasmic encephalitis 1

TMP-SMZ intolerance: Up to 70% of patients who discontinue TMP-SMZ due to adverse reactions can tolerate reintroduction via gradual dose escalation (desensitization) or reduced dosing frequency 1

Monitoring frequency: If unable to monitor CD4+ counts every 3 months, initiate prophylaxis at higher thresholds (CD4+ 200-250 cells/µL for PCP) to avoid missing critical decline 1

Viral load consideration: While most discontinuation studies showed sustained viral suppression, the primary criterion for stopping prophylaxis is CD4+ count >200 cells/µL for ≥3 months, not undetectable viral load 1