Show Summary Details
Page of

Pulmonary disease in the immunocompromised (HIV) 

Pulmonary disease in the immunocompromised (HIV)
Pulmonary disease in the immunocompromised (HIV)

Stephen Chapman

, Grace Robinson

, John Stradling

, Sophie West

, and John Wrightson

Page of

PRINTED FROM OXFORD MEDICINE ONLINE ( © Oxford University Press, 2022. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy and Legal Notice).

date: 05 July 2022

Clinical assessment

Widespread use of antiretroviral therapy (ART) and antimicrobial prophylaxis in HIV has resulted in a longer survival, as well as changes in the nature of respiratory involvement. Respiratory disease remains common in the setting of HIV, and patients should be managed in consultation with an HIV specialist.

Major causes of respiratory disease in the HIV-infected patient are listed on Pulmonary disease in the immunocompromised (HIV) p. [link]. Specific conditions are described separately (e.g. PCP, see Pulmonary disease in the immunocompromised (HIV) pp. [link][link]; TB, see Pulmonary disease in the immunocompromised (HIV) p. [link]). Key management steps are as follows:

Clinical assessment

  • As with other causes of immunocompromise, clinical features of respiratory disease in HIV-infected patients are non-specific: breathlessness, cough, fever, weight loss, and fatigue are common, although chest symptoms are not always present

  • Ask about treatment and compliance with ART and PCP prophylaxis

  • Source of HIV infection may be relevant: Kaposi’s sarcoma occurs particularly in homosexual men and in African men and women; TB and bacterial pneumonia are more common in IV drug users (IVDUs)

  • Travel history may be useful: infection with ‘endemic mycoses’ (histoplasmosis, blastomycosis, coccidioidomycosis) is well recognized in the USA but rare in the UK

  • Careful examination may provide clues to the respiratory condition. Pulmonary Kaposi’s sarcoma is unusual in the absence of disease elsewhere; palatal Kaposi’s sarcoma, in particular, is predictive of pulmonary involvement. Extrapulmonary mycobacterial disease is common and may involve the liver, lymph nodes, pericardium, and meninges.



  • CXR changes are relatively non-specific. Appearances of bacterial pneumonia may be atypical, e.g. diffuse bilateral infiltrates mimicking PCP, and TB may present with focal or diffuse CXR consolidation

  • PCP classically appears as bilateral perihilar infiltrates that progress to alveolar shadowing; more unusual patterns include small nodular infiltrates or focal consolidation; CXR is normal in 10% of cases. Pneumothorax is suggestive of PCP although may also occur with TB

  • Pleural effusion or hilar/mediastinal lymphadenopathy are unusual in PCP and are more suggestive of mycobacterial infection or Kaposi’s sarcoma

  • Common causes of CXR cavitation are PCP, TB (with high CD4 count), P. aeruginosa, fungi, R. equi, Nocardia. Cavitation is relatively unusual in TB occurring late in the course of HIV

  • Common causes of pleural effusion in HIV infection are Kaposi’s sarcoma, parapneumonic effusion, TB, cardiac failure, and lymphoma (including 1° effusion lymphoma).

CD4 count

may be useful in narrowing the differential diagnosis: bacterial infection, including TB, occurs at any stage of disease, although infection is more severe at lower CD4 counts; PCP and atypical presentations of TB occur most commonly at CD4 <200 × 106/L; NTM, Kaposi’s sarcoma, P. aeruginosa pneumonia, and lymphoma occur late in the disease (CD4 <50 × 106/L). A recent increase in CD4 count (following the introduction of ART) may suggest an immune reconstitution inflammatory syndrome (IRIS, see Box 13.1).

Blood cultures

should be taken prior to antimicrobial treatment. Bacteraemia is relatively common with bacterial pneumonia in HIV, particularly with S. pneumoniae infection. Bacteraemic TB may occur in advanced disease.

Other blood

tests Raised inflammatory markers are a non-specific finding.


Induced sputum may assist the diagnosis of PCP and mycobacterial disease. Induced sputum has a sensitivity of about 60% for the diagnosis of PCP. TB is more likely to be smear-negative in the setting of HIV, as cavitation in these patients is less common. Induced sputum should ideally be obtained in a negative-pressure room.

Other cultures

Consider sampling urine, stool, lymph node, or bone marrow in suspected mycobacterial disease, as extrapulmonary disease is common.

CT chest

is useful in looking for evidence of respiratory disease in patients with symptoms, but a normal CXR, and may be helpful in directing invasive diagnostic procedures. CT is also of benefit in the diagnosis and staging of Kaposi’s sarcoma and lymphoma.

Causes of respiratory disease in HIV infection

(commoner causes in bold)



  • Streptococcus pneumoniae

  • Haemophilus influenzae

  • Staphylococcus aureus

  • Gram-negative bacteria, especially Pseudomonas aeruginosa

  • Nocardia asteroides

  • Rhodococcus equi.


  • Mycobacterium tuberculosis

  • Mycobacterium avium-intracellulare

  • Mycobacterium kansasii.


  • Influenza

  • Parainfluenza

  • RSV

  • Herpes simplex

  • Adenovirus

  • CMV.


  • Pneumocystis jirovecii (PCP)

  • Aspergillus spp.

  • Cryptococcus neoformans

  • Endemic mycoses.


  • Strongyloides stercoralis (hyperinfection syndrome).


  • Malignancy

    • Kaposi’s sarcoma

    • Lung cancer

    • Non-Hodgkin’s lymphoma

  • IRIS

  • Drug-induced lung disease

  • Cardiogenic pulmonary oedema (e.g. 2° to cardiomyopathy)

  • HIV-associated PAH

  • Interstitial pneumonitis

    • Non-specific interstitial pneumonitis

    • Lymphocytic interstitial pneumonitis.

Further investigations and treatment

Bronchoscopy and BAL

  • Bronchoscopy and BAL are safe and frequently diagnostic in this patient group and should be considered early in management, particularly in the presence of a diffuse CXR abnormality or following non-diagnostic induced sputum analysis. BAL should also be considered in patients with a localized CXR abnormality that has not responded to a trial of broad-spectrum antibiotics

  • BAL fluid analysis: routine microscopy and culture for bacteria; additional stains and culture for fungi, mycobacteria, Nocardia; silver or immunofluorescence stain for Pneumocystis; cytology, including flow cytometry for malignant cells; respiratory viral serology. Consider additional tests such as Cryptococcus antigen detection or CMV PCR

  • Both Nocardia and Rhodococcus equi stain weakly acid-fast and so may be confused with mycobacteria

  • Kaposi’s sarcoma appears as ‘raised bruises’ in the trachea or bronchi on bronchoscopy; routine biopsy is not usually recommended, as diagnostic yield is low and significant haemorrhage may occur

  • Lung cancer is more common in the setting of HIV, typically affecting relatively young patients with mild to moderate immunocompromise.

Lung biopsy

If bronchoscopy and BAL are non-diagnostic, consider repeat bronchoscopy with TBB or surgical lung biopsy. TBB has a greater sensitivity than BAL, but potentially serious complications (such as pneumothorax or haemorrhage) are significantly more common.


  • Consider broad-spectrum antibiotics and empirical treatment for PCP (high-dose co-trimoxazole, and steroids if the patient is in respiratory failure; see Pulmonary disease in the immunocompromised (HIV) pp. [link][link]). BAL Pneumocystis stains remain positive for up to 2 weeks despite treatment, and so empirical treatment for PCP should not be delayed, pending bronchoscopic confirmation, if the patient is unwell and this diagnosis is suspected

  • In the absence of another identifiable cause, consider empirical treatment directed at TB, pending sputum and BAL culture results

  • Further antimicrobial treatment can be directed at specific pathogens isolated from BAL or biopsy

  • Although isolation of Aspergillus spp. from respiratory samples may reflect contamination or colonization, consider treatment with voriconazole or amphotericin B if isolated from BAL in setting of severe immunocompromise (CD4 <30 x 106/L)

  • Supportive therapy with O2; consider NIV. PCP is the commonest cause of respiratory failure requiring ICU admission in HIV-positive patients and was historically considered to carry a very high mortality rate, although recent studies have reported more favourable outcomes and ICU admission for invasive ventilation may be appropriate for selected patients.