What are the possible pulmonary infections in a patient with Human Immunodeficiency Virus (HIV) and a low CD4+ (Cluster of Differentiation 4+) count?

Pulmonary Infections in HIV Patients with CD4+ Count of 140 cells/μL

At a CD4+ count of 140 cells/μL, this patient is at risk for both common bacterial pneumonias and specific opportunistic infections, particularly Pneumocystis jirovecii pneumonia (PCP), tuberculosis, and bacterial respiratory pathogens, with the differential diagnosis stratified by CD4 thresholds. 1

Infections by CD4+ Count Stratification

Bacterial Pneumonia (Any CD4+ Count)

• Streptococcus pneumoniae and Haemophilus influenzae remain the most common causes of community-acquired pneumonia at any CD4+ level, including at 140 cells/μL 2, 1
• Bacterial pneumonia incidence is elevated compared to HIV-negative populations, with rates of 3.9-7.3 episodes per 100 person-years in the pre-HAART era 2
• Pseudomonas aeruginosa should be considered given the CD4+ count <200 cells/μL, particularly if the patient has pre-existing lung disease, recent hospitalization, or cavitary infiltrates on imaging 2
• Staphylococcus aureus is more common in HIV patients, especially with recent viral infection, injection drug use history, or severe necrotizing pneumonia 2
• Drug-resistant Streptococcus pneumoniae occurs with increased frequency and is associated with higher mortality 2

Pneumocystis jirovecii Pneumonia (CD4+ <200 cells/μL)

• PCP is a critical consideration at CD4+ 140 cells/μL, as prophylaxis should have been initiated at CD4+ <200 cells/μL 2
• PCP can present even without typical radiographic findings when CD4+ counts are this low 2
• If not already on prophylaxis, trimethoprim-sulfamethoxazole (TMP-SMX) one double-strength tablet daily should be initiated immediately 2, 1

Mycobacterium tuberculosis (Any CD4+ Count, Risk Increases <300 cells/μL)

• TB should always be suspected in HIV-infected persons with pneumonia, regardless of CD4+ count, though risk increases significantly below 300 cells/μL 2, 1
• At CD4+ 140 cells/μL, TB can present with atypical radiographic findings 2
• Three sputum specimens for acid-fast bacilli (AFB) smear and culture should be obtained if TB is suspected, with respiratory isolation if hospitalized 2

Fungal Infections (Variable CD4+ Thresholds)

• Cryptococcus neoformans typically causes disease at CD4+ <100 cells/μL, so less likely at 140 cells/μL but possible 3
• Histoplasma capsulatum and Coccidioides species should be considered based on geographic exposure history 3
• Invasive Aspergillus infections can occur but are less common than in other immunocompromised populations 3
• Oral and esophageal Candida infections are common, with esophageal candidiasis typically occurring at CD4+ <200 cells/μL 2

Other Opportunistic Pathogens

• Toxoplasma gondii typically causes disease at CD4+ <100 cells/μL, making it less likely at 140 cells/μL 2
• Cytomegalovirus (CMV) pneumonitis is rare and typically occurs at CD4+ <50 cells/μL 2
• Mycobacterium avium complex (MAC) pulmonary disease is uncommon, as disseminated MAC typically occurs at CD4+ <50 cells/μL 2

Critical Diagnostic Approach

Immediate Workup

• Chest radiograph is mandatory for any HIV patient with respiratory symptoms and CD4+ 140 cells/μL 2
• Blood cultures (two sets) should be obtained given the increased incidence of bacteremia in HIV patients, especially at low CD4+ counts 2
• Sputum Gram stain and culture if good-quality specimen obtainable 2
• Three sputum specimens for AFB smear and culture to exclude TB 2

Additional Testing Based on Clinical Presentation

• Urinary antigen tests for Legionella pneumophila and Streptococcus pneumoniae should be considered 2
• If PCP suspected: induced sputum or bronchoscopy with bronchoalveolar lavage for direct visualization and molecular testing 2
• Pulse oximetry or arterial blood gas to assess oxygenation 1

Common Pitfalls to Avoid

• Never assume only opportunistic infections - bacterial pneumonia remains the most common cause at any CD4+ count 2, 1
• Never delay empiric bacterial coverage while awaiting diagnostic workup, as bacterial pneumonia can progress rapidly 1
• Never overlook TB - it can occur at any CD4+ count and requires specific isolation and treatment considerations 2, 1
• Never use fluoroquinolone monotherapy without excluding TB, as this can mask TB diagnosis, promote resistance, and increase transmission risk 1
• Never forget PCP prophylaxis - if not already prescribed, TMP-SMX should be started immediately at this CD4+ level 2, 1