HIV-associated Pulmonary Disease the HIV/AIDS Clinic and ...– Opportunistic infections –...

Copyright 2018Laurence Huang, M.D.

Classic and Challenging Cases from the HIV/AIDS Clinic and Beyond

Laurence Huang, MDProfessor of Medicine

University of California San FranciscoChief, HIV/AIDS Chest Clinic

Zuckerberg San Francisco General Hospital

HIV, Infectious Diseases, and Global Medicine Division, Division of Pulmonary and Critical Care Medicine


HIV-associated Pulmonary DiseaseThe spectrum of pulmonary diseases in HIV-infected

persons is broad:

• HIV-associated– Opportunistic infections– Neoplasms– Miscellaneous conditions

• Antiretroviral therapy (ART)-associated

• Non HIV-associated

HIV-associated Pulmonary DiseasesOpportunistic Infections Non-infectious NeoplasmsBacteria Pulmonary Kaposi sarcoma

Mycobacteria Pulmonary Non-Hodgkin Lymphoma

Pneumocystis Lung cancer

Fungi

Viruses Miscellaneous ConditionsParasites Lymphocytic interstitial pneumonitis

Nonspecific interstitial pneumonitis

COPD

Pulmonary arterial hypertension

Pulmonary fibrosis

Copyright 2018

Laurence Huang, M.D.

Crothers, Morris and Huang. Chapter 90. Textbook of Respiratory Medicine 2016.

QUESTION:

• I spend the majority of my clinical timeA. Inpatient careB. Critical careC. Outpatient careD. None of the above

Laurence Huang, MD Copyright 2012 ©

Outline• Case-based approach = Interactive (ARS)

• Outpatient focus– Cases from my HIV/AIDS Chest Clinic… and beyond

• “Classic” and challenging cases – old and new– Wide range of backgrounds and experience

• Clinical and management pearls– Professional society, National guidelines


All Slides are in Syllabus… Copyright 2018Laurence Huang, M.D.

Case 1• CD4 < 100 cells/µl

• Several months of increasing dyspnea– Exercise tolerance currently < 1 block– Denies fever; no change in chronic cough

• Physical examination– Lungs – hyperresonant, quiet breath sounds

(bilateral)


Case 1 QUESTION:What is the Most Likely Diagnosis?A. Bacterial pneumonia

B. Pneumocystis pneumonia (PCP)

C. COPD/emphysema

D. Pulmonary Kaposi sarcoma (KS)

E. Other


COPD-Key Points1. HIV-infected individuals are subject to the entire

spectrum of pulmonary disease.

“The presence of HIV infection cannot exclude the possibility that the patient presents with a non-HIV-associated pulmonary disease.”

2. HIV-infected individuals are at increased risk forCOPD (independent of cigarette smoking) andperhaps COPD exacerbations, may develop COPDat an earlier age, and may have an accelerateddecline in their FEV1.

Drummond, MB, Kunisaki, KM and Huang, L. Obstructive lung diseases in HIV: A clinical review

and identification of key future research needs. Semin Respir Crit Care Med 2016;37:277-288. Copyright 2018Laurence Huang, M.D.

COPD-Key Points3. No HIV-specific guidelines. Diagnosis (pulmonary

function tests, PFTs) and treatment ‘identical’ to non-HIV-infected individuals.

3B. An isolated decrease in DLco = most frequent finding in HIV-infected individuals.

If moderate-to-severe COPD and persistent symptoms and/or frequent exacerbations:

4. Triple therapy (inhaled glucocorticoid, LABA, LAMA)associated with decreased exacerbations butincreased risk for pneumonia.

COPD Diagnosis and Management: https://goldcopd.org/COPD Exacerbations: Eur Respir J 2017; 49: 1600791.


Case 2• CD4 = 400 cells/µl

• 5 days of fever, chills, chest pain, cough productive ofpurulent sputum, and dyspnea

• Physical examination– Lungs – Egophony, increased tactile fremitus, and

bronchovesicular breath sounds (right)


Case 2

https://goldcopd.org/

QUESTION:What is the Most Likely Diagnosis?A. Bacterial pneumonia


C. COPD/emphysema


E. Other


Bacterial Pneumonia-Key Points1. Most frequent HIV-associated opportunistic pneumonia

2. Rates are 25-fold higher than among non-HIV-infected• Rates increase as CD4 cell count decreases

• Rates of pneumococcal bacteremia are 50-100-fold higherthan age-matched controls

3. Specific causative agent identified in 40-75%• Streptococcus pneumoniae (40%)

• Haemophilus influenzae (10-15%)

• Staphylococcus aureus (5%) – Beware community MRSA!

• Pseudomonas aeruginosa (5%)Feikin. Lancet Infect Dis 2004;4:445-455.


Bacterial Pneumonia-Key Points4. USPHS Treatment Guidelines (reviewed July 2017)

5. Treatment and outcome (HIV+ vs. HIV-)• No differences in the time to clinical stability, the length of

hospitalization, or mortality

6. Preventive strategies• Combination antiretroviral therapy• Pneumococcal vaccine (CD4>200 cells/µl)• Trimethoprim-sulfamethoxazole (CD<200 cells/µl)• Risk factor modification

• Cigarettes, injection and smoked illicit drugs

Christensen. Clin Infect Dis 2005;41:554-556.

https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportunistic-infection/0

Case 3

• CD4 > 300 cells/µl (HIV RNA undetectable)

• Several months of increasing dyspnea– Exercise tolerance currently < 1 block– Denies fever; no change in chronic cough

• Physical examination– Lungs – hyper-resonant, quiet breath sounds

(bilateral)


Case 3




C. COPD/emphysema


E. Other

Pulmonary Nodules-Key Points

1. Fleischner Society, Radiological Society of NorthAmerica, Updated 2017

* Increase in size mandates diagnostic w/u (e.g., biopsy, surgical removal


Pulmonary Nodules-Key Points

2. No HIV-specific guidelines.

3. Pulmonary nodules are a frequent chest CT findingin HIV-infected individuals

– 25% of 158 HIV-infected individuals Triplette. AIDS 2017;31: 1715-1720.

4. Differential diagnosis of pulmonary nodules in HIV isBROAD



Case 4

• CD4 = 100 cells/µl

• 3 weeks of fever, cough (non-productive), anddyspnea

• Physical examination– Lungs – Bilateral inspiratory crackles– Heart – Tachycardic, no gallops or murmurs


Case 4



C. COPD/emphysema


E. Other


PCP-Key Points1. PCP classically presents with 2-4 weeks of gradually

progressive symptoms– Often HIV identifying (and AIDS-defining) diagnosis

2. CXR with bilateral reticular or granular opacities

3. Chest HRCT useful to rule out PCP – absence ofground-glass opacities

Chest High Resolution CT (HRCT) scanof HIV-infected individual with PCP


PCP-Key Points4. Bronchoscopy with bronchoalveolar lavage (BAL)

remains the gold standard diagnostic procedure– Sensitivity = 89% to >98% (Broaddus 1985, Golden, 1986, Huang 1995)

5. USPHS Treatment Guidelines (updated July 2017)

– Trimethoprim-sulfamethoxazole is the first-line treatment(and prophylaxis) regimen

TMP-SMX drug resistance? Emerg Infect Dis 2004.




• 3 weeks of fever, cough, and dyspnea

• Physical examination– HEENT – mild oral candidiasis, no KS lesions– Lungs – coarse breath sounds– Other – no hepatosplenomegaly, no cutaneous KS

lesions


Case 5 QUESTION:What is the Most Likely Diagnosis?A. Bacterial pneumonia


C. COPD/emphysema


E. Other


Kaposi’s Sarcoma-Key Points1. Pulmonary KS can present in the absence of

mucocutaneous disease“The absence of mucocutaneous KS cannot rule out

(significant) pulmonary KS.”

2. Nevertheless, most patients with pulmonary KS willhave mucocutaneous disease

3. KS seen almost exclusively in MSM


Kaposi’s Sarcoma-Key Points

4. Patients with pulmonary KS may have concurrentopportunistic infection (>25%)

5. Key: MSM andcharacteristic CXR

6. Diagnosis:BAL to r/o OI

Pulmonary KS in tracheaseen on bronchoscopy


Case 6A• CD4 = 400 cells/µl

• 3 weeks of fever, night sweats, cough, anddyspnea– Gradual weight loss

• Physical examination– Lungs – coarse breath sounds (right)


Case 6A

Close-up

QUESTION:What is the Most Likely Diagnosis?A. Tuberculosis (TB)

B. Cryptococcal Pneumonia

C. Endemic Fungal Pneumonia

D. Lung Cancer

E. Other


Case 6B• CD4 = 100 cells/µl

• 3 weeks of fever, night sweats, cough, anddyspnea– Gradual weight loss

• Physical examination– HEENT – cervical lymphadenopathy– Lungs – coarse breath sounds (right)– Other – hepatomegaly


Case 6B

Has anyone seen my

key?




D. Lung Cancer

E. Other


Tuberculosis-Key Points1. Many of the HIV-associated pulmonary diseases

have important extrapulmonary manifestations

2. At CD4 cell count <200, TB often presents withextrapulmonary disease

– Lymph nodes (cervical, supraclavicular, axillary)– Liver– Bone marrow, Genitourinary and Central Nervous

System


Tuberculosis-Key Points3. The “characteristic” radiographic presentation of

TB depends on the CD4 cell count

• “High” CD4 count = upper lung zone disease,often with cavitation

• “Low” CD4 count = diffuse disease (includingmiliary), mid+lower lung zone disease, cavitationless common, hilar and mediastinal adenopathy

• Normal chest radiographs (~10%)Aderaye. Infection 2004;32:333-338.


Tuberculosis-Key Points4. Diagnosis begins with expectorated sputum x 3 sent

for AFB smear and mycobacterial culture– Negative sputum smears are common, particularly among

those with advanced immunocompromise and with non-cavitary disease

– Yield of sputum mycobacterial culture is similar to HIV- and isnot affected by degree of immunocompromise

– Sputum sent for nucleic acid amplification testing becomingfront line diagnostic test

– Pleural fluid (with biopsies) should be sent if +pleural effusion– Extrapulmonary biopsies/samples

Copyright 2018


Tuberculosis-Key Points5. USPHS Treatment Guidelines (updated September 2017)

– Same as for HIV-

– Initial 4-drug regimen: INH, rifampin, ethambutol and

pyrazinamide (+Vitamin B6) x ~2 months (while awaitingcultures and sensitivities)

– If pan-sensitive, stop ethambutol and pyrazinamide and

continue INH and rifampin for a total of 6 months (~4additional months)


Case 7

• CD4 < 50 cells/µl (HIV RNA ~2K copies/ml)

• Cough (occasional phlegm)

• Physical examination– Lungs – clear to auscultation


Case 7





D. Lung Cancer

E. Other

Case 7


Lung Cancer-Key Points

1. Clinical presentation and diagnosis compared to non-HIV-infected patients– HIV-infected significantly younger (median age 50

vs. 68 years)– Adenocarcinoma and squamous carcinoma

predominate– Stage IIIB/IV disease (77%)– Outcomes probably comparable



Case 8• CD4 = 285 cells/µl on HAART (nadir < 100 cells/µl)

• 2-3 months gradually progressive dyspnea, slightcough

– No fever

• Physical examination

– Unremarkable


Case 8 QUESTION:What is the Most Likely Diagnosis?A. Tuberculosis (TB)



D. Lung Cancer

E. Other

Copyright 2018


Hypersensitivity Pneumonitis-Key Points

1. Patient only developed symptoms after

experiencing a rise in CD4 cell count due to HAART

• In hypersensitivity pneumonitis, the underlying

mechanism of disease is host-mediated lung

damage in response to inhaled antigen

2. Increase in reports of sarcoidosis or sarcoidosis-like

disease

Sarcoidosis


ART-associated Pulmonary Disease

Initial CXR Follow-up CXR

IRIS and OI presentation tomorrow @4:45 PM…

Case 9

• CD4 > 300 cells/µl (HIV RNA undetectable)

• Severe shortness of breath, audible “wheezing”

• Physical examination– Lungs – clear to auscultation but diminished breath

sounds



Case 9

CXR after therapeutic intervention




D. Lung Cancer

E. Other


Life-Threatening Tracheal Stenosis!Immune Reconstitution-Key Points

1. Immune Reconstitution Syndrome– Describes paradoxical worsening of opportunistic

infection with concurrent treatment of HIV and OI– days to months

2. Pulmonary diseases– TB, pulmonary MAC, PCP, Cryptococcus– Presents with worsening, recurrent (occasionally

new) symptoms and CXR findings

Hirsch. Clin Infect Dis 2004;38:1159-1166.

Lawn. Lancet Infect Dis 2005;5:361-373.


Immune Reconstitution-Key Points

3. Diagnosis of EXCLUSION– Non-adherence– Drug resistance– Concurrent or superimposed process

4. Related to immune response to residual organismand/or antigen

Hirsch. Clin Infect Dis 2004;38:1159-1166.Lawn. Lancet Infect Dis 2005;5:361-373.

Copyright 2018



• 2 weeks of fever, cough (non-productive), anddyspnea

– More recently, cough productive of purulent sputum

• Physical examination

– Lungs – bilateral inspiratory crackles and focalfindings (egophony, decreased breath sounds)


Case 10 QUESTION:What is the Most Likely Diagnosis?A. Tuberculosis (TB)



D. Lung Cancer

E. Other


PCP and Bacterial Pneumonia-Key Points

1. HIV-infected patients may present with more thanone concurrent disease– PCP diagnosed in 14 of 111 bacterial pneumonia

cases (12.6%) Afessa. Chest 2000.

– Bacterial infection complicates PCP in ~10%

2. Beware: Concurrent diseases that present withidentical clinical and radiographic features


PCP and Cryptococcus

PCP and Cryptococcal pneumonia most often present with bilateral reticular or granular opacities


SUMMARYHIV-associated Pulmonary Disease

The spectrum of pulmonary diseases in HIV-infected persons is broad:

• HIV-associated– Opportunistic infections (BP, TB, PCP)– Neoplasms (KS, NHL, lung cancer)– Miscellaneous conditions (COPD, LIP, NSIP, PAH)

• ART-associated (HP, sarcoidosis, TB-IRIS, PCP)

• Non HIV-associated (Pulmonary nodules? Tracheal stenosis)


SUMMARYHIV-associated Pulmonary Disease

• “Classic” presentations of HIV-associatedpulmonary diseases– Presentations vary and overlap

• Patients may present with more than oneconcurrent pulmonary disease (PCP and BP)

• New era of ART-related pulmonary conditionsTHANKS!

HIV-associated Pulmonary Disease the HIV/AIDS Clinic and ...– Opportunistic infections –...

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