12. HIV and Shortness of Breath

Overview

In the age of ART, the incidence of AIDS-related opportunistic infections (OIs) is decreasing and the prevalence of chronic illnesses, such as COPD and CAD, is rising. 

Differential Diagnosis

  • Despite the broad differential for shortness of breath in an HIV-positive patient, ~ 85% of all pulmonary infections in this population are caused by three etiologies: bacterial pneumonia (45%), PCP (30%), and TB (10%)
  • Infectious: influenza, community-acquired bacterial pneumonia, PCP, TB, other fungal infections (Coccidiodes spp, Histoplasma capsulatum, Crytpococcus), and IRIS (ARVs initiated < 3 months)
    • Bacterial pneumonia (especially due to S. pneumoniae and H. influenzae) and influenza are the most frequent HIV-associated pulmonary infections reported
  • Non-infectious causes: lymphoma, Kaposi sarcoma, lung cancer, and COPD
  • Non-pulmonary causes: CAD, pulmonary artery hypertension, HIV cardiomyopathy, lactic acidosis from treatment with nucleoside analogues (rare), pulmonary embolism, and methemoglobinemia secondary to dapsone

The differential depends on the CD4 count:

  • <500: bacterial pneumonia, increased incidence of non-tuberculosis mycobacterial infections (e.g. M. kansasii)
  • <200: bacterial pneumonia more often accompanied by bacteremia and sepsis. Greater risk of extra-pulmonary or disseminated M. tuberculosis infection. Increased concern for Pneumocystis and Cryptococcus neoformans pneumonia
  • <100: consider pulmonary involvement with Kaposi sarcoma and Toxoplasma gondii
  • <50: occurrence of disease from endemic fungi (Histoplasma capsulatum and Coccidiodes spp), and non-endemic fungi (Aspergillus spp.)

Evaluation

  • The clinical history can provide clues:
    • Fever < 7 days suggests bacterial pneumonia (odds ratio 6.6)
    • Fever > 7 days suggests mycobacterium tuberculosis (odds ratio 3.6)
  • If the prior CD4 count is unknown, it can be sent in the acute setting but note CD4 levels can be acutely low in patients with active infections
  • The CXR findings can be helpful:
    • A lobar infiltrate suggests bacterial pneumonia (odds ratio 5.8)
    • Diffuse, bilateral, symmetric interstitial infiltrates suggests PCP (odds ratio 10.2)
  • In addition to the usual evaluation for shortness of breath, additional workup may depend on the organisms being considered:
    • PCP: LDH, Beta-D-glucan, induced sputum for PCP; gold-standard for diagnosis is bronchoscopy
    • Fungal: serum CrAg, urinary histoplasmosis antigen, cocci immunodiffusion/complement fixation
    • Viral: PCR assays by nasal swab
    • Tuberculosis: sputum AFB smear/culture and GeneXpert

Note, patients with HIV and acute pulmonary disease may warrant early CT scanning, pulmonary consultation, or bronchoscopy.

Pneumocystis jirovecii pneumonia (PCP):

  • PCP is still the most common opportunistic infection in HIV patients
  • Uncommon in those on prophylaxis (failure rate ~5% on TMP-SMX but ~15% on other regimens)
  • Suspect PCP if there is a subacute (i.e. days to weeks) onset of fever, non-productive cough, and dyspnea
  • Up to 50% will have a normal pulmonary examination
  • The CXR classically shows bilateral interstitial opacities. 10-20% will have a normal CXR. Pleural effusions are not associated with PCP and should increase suspicion for bacterial or fungal pneumonia, TB, or Kaposi sarcoma
  • Elevated serum LDH with >80% sensitivity, but poor specificity for PCP. Markedly elevated LDH or increasing LDH despite appropriate therapy are poor prognostic markers
  • Beta-D-glucan has a sensitivity of >90% but specificity of only 65-90%
  • Chest CT (noncontrast) may be useful in suspected PCP with normal or unchanged CXR, though patchy GGO are non-specific; useful in ruling out PCP (NPV ~100%)
  • 95% of patients with PCP have CD4 count < 200, but PCP can occur in those with CD4 > 200, especially if the patient is asplenic, pregnant, or postpartum

Management

  • Use clinical suspicion and exposures to guide empiric treatment
  • Empiric treatment for bacterial CAP is the same in HIV and non-HIV patients
  • PCP: preferred treatment regardless of degree of illness is TMP-SMX (Septra®, Bactrim®)
    • Recommended duration of therapy 21 days
    • Oral or IV: TMP/SMX (dose by TMP component at 15 -20 mg/kg/day divided q6 – 8h)
      • Mild-moderate disease with TMP-SMX allergy: atovaquone or childamycin + primaquine (must check G6PD status before giving primaquine)
      • Severe disease with TMP-SMX allergy: clindamycin + primaquine (first choice) or IV pentamidine
    • Initiate steroids for suspected severe PCP based on room-air PaO2 < 70 mmHg or A-a gradient > 35
      • May prevent the inflammation (and associated hypoxia) associated with initiating PCP treatment
      • Dose: prednisone 40 mg PO BID x 5 days, 40 mg PO DAILY x 5 days, then 20 mg PO DAILY x 11 days
      • Initiate as early as possible, ideally before the first dose of antibiotics
  • Strongly consider airborne isolation and testing for TB
  • Avoid fluoroquinolones if high suspicion for TB as this can breed resistance over time

Key Points

  • Bacterial pneumonia is the most frequent HIV associated pulmonary disease reported, but the differential broadens as the CD4 count decreases
  • If uncertain as to whether to start steroids for PCP obtain an ABG

Kaplan JE, Benson C, Holmes KK, et al.  Guidelines for prevention and treatment of opportunitic infections in HIV-infected adults and adolescents. MMWR 2009 58(RR04):1-198.

Huang L Pulmonary manifestations of HIV.  HIVInSite January 2009

Feldman C.  Pneumonia associated with HIV infection. Curr Opin Infect Dis 2005,18:165-170.

Thomas CF Jr., Limper AH. Pneumocystis pneumonia. N Engl J Med 2004;350:2487-2495

Zaman MK, White DA. Serum lactate dehydrogenase levels and Pneumocystis carinii pneumonia. Diagnostic and prognostic significance. Am Rev Respir Dis 1988;137(4):796-800.

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on June 1, 2020).

Key words: Pneumocystis pneumonia, pneumonia-HIV, PCP-treatment, IRIS