What opportunistic infections are associated with a low CD4 (Cluster of Differentiation 4) count in a patient with HIV (Human Immunodeficiency Virus)/AIDS (Acquired Immune Deficiency Syndrome)?

CD4 Count Thresholds and Associated Opportunistic Infections in HIV/AIDS

Initiate prophylaxis for Pneumocystis pneumonia (PCP) when CD4 count drops below 200 cells/μL, for toxoplasmosis below 100 cells/μL (if IgG positive), and for Mycobacterium avium complex (MAC) below 50 cells/μL. 1

Critical CD4 Thresholds for Specific Opportunistic Infections

CD4 <200 cells/μL

• Pneumocystis jirovecii pneumonia (PCP) is the hallmark infection at this threshold and requires prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) 800mg/160mg double-strength tablet three times weekly 1
• PCP prophylaxis should also be initiated if unexplained fever >100°F for ≥2 weeks or oropharyngeal candidiasis occurs, regardless of CD4 count 2
• Oral and esophageal candidiasis becomes increasingly common below this threshold 1, 3
• Patients with CD4 <200 cells/μL are at high risk even when chest radiographs appear normal 4

CD4 <100 cells/μL

• Toxoplasma gondii encephalitis requires prophylaxis in patients with positive IgG antibodies for Toxoplasma 1
• Cryptococcosis (particularly cryptococcal meningitis) typically occurs at this level 1
• Histoplasmosis and coccidioidomycosis become more frequent 1
• Risk for disseminated fungal infections increases substantially 4

CD4 <50 cells/μL

• Disseminated Mycobacterium avium complex (MAC) requires prophylaxis with azithromycin 1200 mg orally once weekly 1
• Continue MAC prophylaxis until CD4 count recovers to ≥100 cells/μL for ≥3 months duration after ART initiation 1
• This represents the most severe immunosuppression with highest risk for multiple concurrent opportunistic infections 4

Infections That Occur at Any CD4 Level

• Tuberculosis can occur at any CD4 count, though risk increases significantly when CD4 <300 cells/μL 1
• Herpes zoster (shingles) and pneumococcal infections can occur even with CD4 >200 cells/μL 1
• These infections do not follow the typical pattern of severe immunosuppression-related opportunistic infections 2

Prophylaxis Regimens by CD4 Threshold

For PCP (CD4 <200 cells/μL):

• First-line: TMP-SMX double-strength tablet three times weekly provides cross-protection against toxoplasmosis and many bacterial infections 2, 1
• Alternative: Dapsone 100 mg orally daily if TMP-SMX cannot be tolerated 2, 1
• Alternative with toxoplasmosis coverage: Dapsone plus pyrimethamine plus leucovorin 2

For Toxoplasmosis (CD4 <100 cells/μL with positive IgG):

• TMP-SMX provides dual coverage for both PCP and toxoplasmosis 2
• Dapsone plus pyrimethamine regimens also protect against toxoplasmosis 2

For MAC (CD4 <50 cells/μL):

• Azithromycin 1200 mg orally once weekly is the preferred regimen 1

Critical Considerations for Prophylaxis Management

When to Base Prophylaxis Decisions:

• Use the lowest CD4 count ever recorded (nadir CD4) to determine need for prophylaxis, not the most recent count elevated by antiretroviral therapy 2
• This approach remains recommended until more data on immune reconstitution becomes available 2

When to Discontinue Prophylaxis:

• PCP prophylaxis: Discontinue when CD4 >200 cells/μL for ≥3 months on ART with sustained virologic suppression 1
• Toxoplasmosis prophylaxis: Discontinue when CD4 >200 cells/μL for ≥3 months on ART 1
• MAC prophylaxis: Discontinue when CD4 >100 cells/μL for ≥3 months on ART with sustained virologic suppression 1

Common Opportunistic Infections by Frequency

Based on contemporary data, the most frequently observed opportunistic infections in order of prevalence are:

1. Tuberculosis (9.72%) - most common overall 3
2. Oral candidiasis (5%) - second most common 3
3. Diarrhea (3.3%) - often due to cryptosporidiosis, microsporidiosis, or CMV colitis 3
4. Pneumocystis pneumonia - remains a leading cause of morbidity despite prophylaxis availability 2
5. Cytomegalovirus (CMV) disease - particularly retinitis and colitis in advanced disease 5

Critical Pitfalls to Avoid

• Never discontinue prophylaxis prematurely - ensure sustained CD4 recovery for the specified duration (3 months) before stopping 1
• Do not rely solely on absolute CD4 counts - CD4 percentage is more consistent with successive measurements due to 10% diurnal variation and 13% week-to-week variation in absolute counts 4
• Do not assume normal chest radiographs exclude opportunistic infections in patients with CD4 <200 cells/μL 4
• Recognize that AIDS patients may not tolerate TMP-SMX in the same manner as non-AIDS patients, with greatly increased incidence of rash, fever, leukopenia, and elevated transaminases 6
• Monitor for hyperkalemia when using TMP-SMX, particularly in patients with renal insufficiency or those on other potassium-elevating medications 6

Antiretroviral Therapy as Primary Prevention

• Highly active antiretroviral therapy (HAART) is the most effective approach to preventing opportunistic infections by suppressing HIV replication and increasing CD4 counts 1
• ART reduces the risk of developing HIV-associated opportunistic infections and malignancies by restoring immune function 2
• Consider ART for all HIV-infected persons regardless of CD4 count in contemporary practice 1