1. 1 Respiratory Diseases in HIV-infected Patients HAIVN Harvard Medical School AIDS Initiative in Vietnam

2. 2 Learning Objectives By the end of this session, participants should be able to: Identify the most common causes of respiratory diseases in HIV patients Outline differential diagnoses for common respiratory syndromes Explain how to diagnose and treat respiratory diseases in HIV patients

3. 3 Introduction Bacterial pneumonia, TB, and PCP are the top three causes of respiratory infections in HIV infected patients in Vietnam and other developing countries The likelihood of different etiologies depends on the CD4

4. 4 Common Etiologies of Lung Disease Infectious Bacterial infections Mycobacterial infections Viral infections Non infectious Kaposi’s sarcoma Lymphoma LIP in children Other: Congestive heart failure Asthma and COPD Lung cancer

5. 5 Etiology of Lung Disease by CD4 CD4 > 200CD4 < 200  Bacterial Bronchitis Strep pneumoniae H. influenza Moraxella Klebsiella Pseudomonas  TB  Influenza  TB  PCP  Bacterial  MAC  Fungus Cryptococcus Penicillium  Viral: CMV

6. 6 Diagnostic Approach

7. 7 Three Steps for Diagnosing Respiratory Infections 1.Taking a history 2.Conducting a physical examination 3.Performing diagnostic testing

8. 8 History: What to Look for? Duration and nature of pulmonary symptoms Other complaints (fever) History of pulmonary or cardiac diseases Current medications (prophylaxis) HIV stage, TLC, and/or CD4 count

9. 9 Diagnostic Clues from History Bacterial Pneumonia TBPCP CD4 AnyAny, more likely if CD4 falls <200 (usually) Onset Acute (few days) Sub-acute (days to weeks) Symp- toms Fever Productive cough  Systematic symptoms Cough > 2-3 weeks Fever Weight loss Night sweats Dry cough Shortness of breath

10. 10 Physical Examination General Considerations Inspection Palpation Percussion Auscultation

11. 11 Diagnostic Testing Chest X Ray CBC Sputum Smear for AFB, gram stain Culture of sputum, blood Measurement of oxygen saturation

12. 12 Overview of Three Most Common Lung Diseases Among PLHIV

13. 13 Bacterial Pneumonia (1) History: Fever Productive cough CD4 high or low Chest pain CXR: lobar consolidation Etiology: Pneumococcus H. influenzae S. aureus

14. 14 Bacterial Pneumonia (2) Treatment: OutpatientIn-patient Azithromycin Erythromycin Amoxicillin/clavulanate Levofloxacin (if TB not suspected) Third-generation cephalosporin +/- erythromycin

15. 15 Pneumocystis jiroveci Pneumonia (PCP) (1) Clinical manifestations include: gradual onset of shortness of breath dry cough fever Lung sounds may be clear or have faint crackles Hypoxia is common Elevation of LDH is common but nonspecific CD4 <200 (though occasionally higher)

16. 16 Pneumocystis jiroveci Pneumonia (PCP) (2) Typical CXR bilateral diffuse infiltrations Atypical CXR normal result blebs and cysts lobar infiltrates Suggestive CXR pneumothorax

17. 17 PCP Diagnosis (1) Diagnosis can be made clinically Empiric treatment should be started if the diagnosis is suspected Definitive diagnosis is made by sputum smear and stain Fluorescent stain

18. 18 PCP Treatment Condition, Medication Treatment regimen Trimethoprim (TMP)- sulfamethoxazole (CTX) 15-20 mg/kg/day (of TMP) for 3 weeks For severe cases, add prednisone (for 21 days) 40 mg twice daily for 5 days, then: 40 mg daily for 5 days then: 20 mg/day for 11 days Then, chronic suppressive therapy: CTX 160/800mg daily Discontinue when CD4 >200 for 6months on ARV National Treatment Protocol

19. 19 Tuberculosis (1) CD4 > 500 “Typical” presentation: Fever Cough Weight loss Bloody sputum CD4 < 200 “Atypical” presentation: fever of unknown etiology weight loss minimal cough Extra-pulmonary disease more likely Signs and Symptoms of Pulmonary TB

20. 20 Tuberculosis (2) Diagnosis: Clinical symptoms CXR Sputum AFB smear Bronchoscopy where available Tissue biopsy (lymph nodes) Right upper lobe infiltrate

21. 21 Tuberculosis (3) National Treatment Protocol ConditionTreatment Regimen New treatment 4RH Requires DOTS in maintenance phase 2S(E)HRZ/6HE or 2S(E)RHZ/4RH Re-treatment Severe cases2SHRZE/1HRZE/5H 3 R 3 E 3 For children2HRZE/4HR or 2HRZ/4HR

22. 22 Chest X-ray Interpretation High CD4 counts are usually associated with typical appearance on CXR Low CD4 levels are frequently associated with atypical or even normal findings on x-rays This is especially true for TB

23. 23 CXR Pattern (1) What is the etiology? Bacterial causes S.pneumoniae Haemophilus influenzae Tuberculosis Describe the finding Right middle lobe consolidation

24. 24 CXR Pattern (2) What is the etiology? PCP TB Viral infection (Influenza) Cryptococcus P. marneffei Describe the finding Diffuse interstitial infiltrates

25. 25 CXR Pattern (3) What is the etiology? TB Lymphoma Fungal Describe the finding Mediastinal lymphadenopathy

26. 26 CXR Pattern (4) What is the etiology? TB Fungal Describe the finding Nodular or miliary pattern

27. 27 Case Studies from Viet Nam

28. 28 Dung, Male (1) Has a fever, cough with bloody sputum x 3 months, 8 kg weight loss CD4 = 280 Not yet on ARVs What are the CXR findings? Bilateral upper lobe infiltrates, possibly with cavitation

29. 29 Dung, Male (2) What diagnostic testing is needed? Sputum AFB and Gram stains Result: 3/3 AFB + What is the best treatment? Treat TB first, then start ARV after once the patient is clinically improving and tolerating TB therapy

30. 30 Quoc, Male, 30 Year Old (1) HIV+, TLC = 1,000 Fever, cough, chest pain Weakness for 1 month Sputum AFB at district OPC reported as negative What are the CXR findings? Right upper lobe infiltrate with middle/lower lobe infiltrate Mediastinal lymph nodes

31. 31 Quoc, Male, 30 Year Old (2) What is the differential diagnosis? TB Bacterial pneumonia What diagnostic testing would you do? Sputum for Gram stain and repeat AFB Lymph node aspirate (if present) CD4 Results: Repeat sputum AFB positive 1/3 CD4 = 150

32. 32 Long, Male (1) Fever, cough and shortness of breath for 1 month CD4 = 150 What are the CXR findings? Right infiltrate with large right pleural effusion

33. 33 Long, Male (2) What is the differential diagnosis? TB, bacterial pneumonia How should Long be treated? Patient was started on antibiotics for bacterial pneumonia and after 1 week had sputum AFB+ He continued antibiotic treatment for 10 days and started TB treatment The patient responded well

34. 34 Key Points The etiology and manifestations of lung disease vary depending on CD4 count Common causes are bacterial pneumonia, TB, and PCP TB is most common cause of lung disease and most prevalent OI among PLHIV X-rays are often atypical in HIV positive patients, especially when CD4 is low

35. 35 Thank you! Questions?