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Journal of The
Association of
Physicians of India
■ Vol. 67
■ January 2019
Pulmonary Involvement in People
Living with HIV (PLHIV)
• Guide – Dr KALINGA B
E
• Student – Dr MEDINI
HIV  HIV is an enveloped positive stranded RNA virus that
measures 120 nm in diameter
 lipid bilayer with uniformly arranged 72 spikes or knobs of
glycoprotein – gp 120 and gp 41 (HIV-1)/gp 36 (HIV-2).
 The virion gp120 located on the virus surface contains the
binding site for cellular receptor(s).
 The two plus stranded RNA molecules are embedded in a
protein capsid (p24) together with certain viral enzymes
(viral RNA-dependent DNA polymerase (Pol, also called the
reverse transcriptase, RT (p66, p51) and nucleocapsid
proteins (p9, p7).
 The capsid (p24) is surrounded by a matrix
layer (p17) that in turn is enclosed in lipid bi-layer, the
envelope
Replication
cycle
OPPORTUNISTIC INFECTIONS IN HIV
CD4 COUNT(/mm2) INFECTIOUS DISEASES
>500 CANDIDA VAGINITIS
200 TO 500 PNEUMOCOCCAL PNEUMONIA
PULMONARY TUBERCULOSIS
OROPHARYNGEAL CANDIDIASIS
CRYPTOSPORIDIOSIS
KAPOSI SARCOMA
ORAL HAIRY LEUKOPLAKIA
<200 PNEUMOCYSTIS JIROVECI
DISSEMINATED HISTOPLASMOSIS
CD4 COUNT(/mm2)
a
INFECTIOUS DISEASES
MILIARY/EXTRAPULMONARY TB
PML
<100 HERPES SIMPLEX
TOXOPLASMOSIS
CRYPTOCOCCOSIS
MICROSPORIDIOSIS
CANDIDA ESOPHARYNGITIS
<50 DISSEMINATED CMV
MAC
PULMONARY INFECTIONS
 Pulmonary system is most commonly involved system in PLHIV.
 In PLHIV immunity is suppressed, hence lungs are prone for infectious
and non infectious pulmonary disease.
 Pneumonia is most common pulmonary manifestation followed by
tuberculosis and pneumocystis jirovecii pneumonia.
Bacterial pneumonia
 The most common identified pathogen in HIV related bacterial pneumonia
is Staphylococcal followed by Hemophilus influenza.
 Gram negative bacilli and Staphylococcus aureus assume increasing
importance as immunosuppression worsens, due to neutrophil dysfunction.
 Pseudomonas aeroginosa has been associated with neutropenia and CD4
count <50 cells/mm.
 Pneumococcal vaccine is recommended in all HIV patients who have CD4
count greater than 200 and influenza vaccine annually regardless of CD4
count.
Pneumocystis jiroveci
 Hallmark of AIDS
 Approx 30 % of HIV associated
PCP occur in people who are
unaware of their HIV status
 Risk is high-
1. previous bout of PCP
2.CD4 <200
Clinical features-
 Progressive dyspnea
 Non productive cough
 Characteristic retrosternal chest pain which is worse on inspiration(sharp
or burning)
 Fever
 Unexpected weight loss
Investigations
 Sample- induced sputum (55%) and BAL(95%), transbronchial biopsy and
open lung biopsy
 CBC- mild leucocytosis
 Elevated LDH
 ABG- increase in arterial alveolar gradient
 Recent- PCR has been used to detect specific DNA sequences
Demonstration on tissue specimens
Methanamine silver stained broncheoalveolar
lavage (BAL) fluid
Transbronchial lung biopsy stained with
hematoxylin and eosin shows eosinophilic alveolar
IMAGING
Chest xray-
 either a normal film or a faint
perihilar interstitial infiltrate
 Lobar infiltrates or pleural
effusion less commonly
CT-
 patchy ground glass appearance
TREATMENT OF PNEUMOCYSTOSIS
PRIMARY AND SECONDARY PROPHYLAXIS
Pulmonary tuberculosis
 About 1/3 of death all AIDS related death associated with tuberculosis.
 Tuberculosis is the primary cause of death in 10-12% HIV infection.
 About 60-80% HIV infected patient With Tuberculosis have pulmonary
disease, 30-40% have extra pulmonary involvement.
Clinical features
High CD4
 Fever
 Cough
 Dyspnea on exertion
 Weight loss
 Night sweats
Low CD4
 Disseminated disease
Comparison between PTB in HIV Vs Non HIV
IMAGING
 HIGH CD4
Cavitary apical lesion of upper
lobes
 LOW CD4
Diffuse and lower lobe bilateral
reticulonodular infiltrates
consistent with miliary spread,
pleural effusions,
hilar/mediastinal adenopathy
Recommendations
 Therapy of TB is generally same in the HIV infected person as in HIV
negative patient.
 Adjusted dose of Rifabutin are required when treating TB in the sitting of
HIV
 Initiation of ART and/or anti TB therapy may be associated with clinical
deterioration due to IRIS
 Initiation of ART delayed in antiretroviral naïve patients with CD4 above
50 until 2-4 weeks following treatment for TB
 For patients <50 CD4 the benefits of ART outweigh the risks of ART
IRIS
 Immune reconstitution inflammatory syndrome.
 Paradoxical worsening of an existing clinical condition or abrupt
appearance of a new clinical finding (unmasking) is seen following
initiation of ART.
 Occurs 2 weeks to 2 years following the initiation of therapy.
 CD4 count <50/microL who experience precipitous drop in viral load.
 Reflects immediate improvement in immune function that occur as levels
of HIV RNA drop and immunosuppressive effects of HIV are controlled.
HISTOPLASMA
 Histoplasmosis most commonly presents
with disseminated disease in CD4 <150
 Fever weight loss, adenopathy and
mucosal lesions
 It can also produce sepsis syndrome with
hypotension and MODS
 Presence of hilar or mediastinal
lymphadenopathy may help as a
distinguishing factor
 Treatment – liposomal Amphotericin B
Itraconazole
Non infectious pulmonary complications
KAPOSIS SARCOMA
 Endothelial cells latently infected with HHV8 activated
Angiogenesis leading to vascular malignancy
 Pulmonary KS may be asymptomatic even in patients with extensive
abnormalities on CXR
 80% of patient with pulmonary KS have cutaneous lesions
 Direct visualization of purplish plaques on bronchoscopy
 Chest x ray bilateral pulmonary lower lobe infiltratesthat obscure margins
of diaphragm and mediastinum
 Pleural effusion in 70% cases of KS
Treatment
 Optimizaion of ART
 Chemotherapy with doxorubicin, bleomycin and vinblastine
HIV PAH
 0.5 %
 Shortness of breath, syncope, chest pain, signs of right heart failure and
right sided cardiomyopathy
 Most common hypothesis- alteration in pulmonary cytokine profile and
increased expression of vasoactive substances like endothelin 1
 Management- Prostaglandin agonist – epoprostenil
Diuretics
Sildenafil
Aims and Objectives
 1. To study pulmonary involvement in peoples living with HIV diagnosed
by ELISA method.
 2. To study radiological findings in lungs of PLHIV with pulmonary disease
by chest x ray, High resonance computed tomography, ultrasonography of
thorax etc.
 3. To study co-relationship between CD4 count and pulmonary disease in
PLHIV.
Material and Methods
Methodology
 This is descriptive clinical study with cross sectional design with 100 HIV
positive patients to study pulmonary involvement in people with HIV
(PLHIV) patient.
Source of Data
 The study was conducted in Dr. V.M. Government Medical college,
Solapur, Maharashtra, India, Present study was carried out on PLHIV with
pulmonary involvement.
 The period is from Dec.2012 to Nov. 2014. Present study was conducted
after NACO permission
Inclusion Criteria
 1. Age>13 yrs
 2. HIV positive patient diagnosed by ELISA method
 3. Patient having pulmonary symptoms
Exclusion Criteria
 1. Age <13 yrs
 2. HIV negative patient
 3. PLHIV with only upper respiratory tract infection
 4. PLHIV not willing to give consent
Following investigations were
done
 1. Chest x ray PA view of all patients
 2. Sputum for AFB -1 sample on admission, 2 sample on early morning
 3. Sputum for gram staining
 4. Sputum for pneumocystis jiroveci for GMS stain.
 5. Sputum for culture and sensitivity
 6. PAS Stain for mycobacterium avium complex
 7. Pleural fluid study i.e. cyto, biochem or in suspected cases pleural fluid
ADA
 8. Ultrasonography of thorax in case of pleural effusion to rule out
pulmonary involvement.
 9. HRCT thorax in suspected patient in whom chest X-ray PA view is
normal.
 10. Fine needle aspiration cytology ( FNAC ) of lymph node in patient
present with lymphadenopathy.
 11. Blood culture, LFT, RFT, CBC, CD4 count in All patient.
 12. ESR
Observations and Results
 71% were tuberculosis patient, followed by
 22% were bacterial pneumonia patient followed by
 7% were pneumocystis jirovecii pneumonia
Disease wise distribution of study
population
DISEASE NO OF PATIENTS PERCENTAGE
TUBERCULOSIS 71 71
PNEUMONIA 22 22
PCP 7 7
MAC 0 0
MALIGNANCY 0 0
CXR PATTERN IN TB
 Consolidations in 33.80% patient
 Pleural effusion 23.94% patient
 Fibro nodular infiltrate 16.90% patient
 Cavitatory lesion in 16.90 % patient
 Miliary tuberculosis in 14.08%,
 Bilateral extensive tuberculosis 14.08%
 Pneumothorax in 8% patient
Chest X-ray findings in pulmonary
tuberculosis patient
CXR FINDING NO OF TB PATIENTS (%)
CONSOLIDATION 24 (33.8%)
PLEURAL EFFUSION 17 (24%)
PNEUMOTHORAX 6 (8%)
B/L EXTENSIVE TB 10 (14.1%)
FIBRONODULAR INFILTRATE 12 (16.9%)
MILIARY TB 10 (14.1%)
CAVITATORY LESIONS 12 (16.9%)
CXR PATTERN IN PNEUMOCYSTIS
JIROVECI
 95.5 % patient showed ground glass haziness on chest x ray out of
which
 33.33% patient had 1 zone involvement
 66.66% patient had >1 zone involved
 83.33% patient had lower zone involvement followed by
 16.66% patient had upper zone
 Parahilar Opacity in 71.42% patient
Chest X-ray findings in Pneumocystis jirovecii
pneumonia
Co-relation between CD4 count and
pulmonary disease
CD4 count No. of bacterial
pneumonia
patient
No. of
tuberculosis
patient
No. of PJP
patient
>500 5 (22.76%) 1 (1.4%) 0 (0%)
201-500 9 (40.90%) 26 (36.61%) 0 (0%)
151-200 3 (13.63%) 14 (19.71%) 0 (0%)
101-150 10 (04.54%) 10 (14.08%) 1 (14%)
50-100 0 (0%) 12 (16.09%) 1 (14%)
<50 4 (18.18%) 8 (11.26%) 5 (72%)
Summary and Conclusion
1. In present study prevalence of tuberculosis was maximum in patient
followed by bacterial pneumonia and pneumocystis jiroveci pneumonia
respectively.
2. In present study prevalence of
 Bacterial pneumonia was maximum in CD4 count >200cells/micro lit,
 Tuberculosis was maximum in CD4 count between 150-500/micro lit,
 Pneumocystis jiroveci pneumonia was max in CD4 count <50/micro lit.
LIMITATIONS
 Short duration of study.
 Sample size was less i.e only 100 participants were considered for the
study and the results of which could not be extrapolated to the general
population.
References
 Harrison’s textbook of internal medicine, 20th edition.
 API textbook of internal medicine, 11th edition.
THANK YOU

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Pulmonary involvement in peoples living with HIV

  • 1. Journal of The Association of Physicians of India ■ Vol. 67 ■ January 2019 Pulmonary Involvement in People Living with HIV (PLHIV) • Guide – Dr KALINGA B E • Student – Dr MEDINI
  • 2. HIV  HIV is an enveloped positive stranded RNA virus that measures 120 nm in diameter  lipid bilayer with uniformly arranged 72 spikes or knobs of glycoprotein – gp 120 and gp 41 (HIV-1)/gp 36 (HIV-2).  The virion gp120 located on the virus surface contains the binding site for cellular receptor(s).  The two plus stranded RNA molecules are embedded in a protein capsid (p24) together with certain viral enzymes (viral RNA-dependent DNA polymerase (Pol, also called the reverse transcriptase, RT (p66, p51) and nucleocapsid proteins (p9, p7).  The capsid (p24) is surrounded by a matrix layer (p17) that in turn is enclosed in lipid bi-layer, the envelope
  • 4.
  • 5. OPPORTUNISTIC INFECTIONS IN HIV CD4 COUNT(/mm2) INFECTIOUS DISEASES >500 CANDIDA VAGINITIS 200 TO 500 PNEUMOCOCCAL PNEUMONIA PULMONARY TUBERCULOSIS OROPHARYNGEAL CANDIDIASIS CRYPTOSPORIDIOSIS KAPOSI SARCOMA ORAL HAIRY LEUKOPLAKIA <200 PNEUMOCYSTIS JIROVECI DISSEMINATED HISTOPLASMOSIS
  • 6. CD4 COUNT(/mm2) a INFECTIOUS DISEASES MILIARY/EXTRAPULMONARY TB PML <100 HERPES SIMPLEX TOXOPLASMOSIS CRYPTOCOCCOSIS MICROSPORIDIOSIS CANDIDA ESOPHARYNGITIS <50 DISSEMINATED CMV MAC
  • 7. PULMONARY INFECTIONS  Pulmonary system is most commonly involved system in PLHIV.  In PLHIV immunity is suppressed, hence lungs are prone for infectious and non infectious pulmonary disease.  Pneumonia is most common pulmonary manifestation followed by tuberculosis and pneumocystis jirovecii pneumonia.
  • 8. Bacterial pneumonia  The most common identified pathogen in HIV related bacterial pneumonia is Staphylococcal followed by Hemophilus influenza.  Gram negative bacilli and Staphylococcus aureus assume increasing importance as immunosuppression worsens, due to neutrophil dysfunction.  Pseudomonas aeroginosa has been associated with neutropenia and CD4 count <50 cells/mm.  Pneumococcal vaccine is recommended in all HIV patients who have CD4 count greater than 200 and influenza vaccine annually regardless of CD4 count.
  • 9. Pneumocystis jiroveci  Hallmark of AIDS  Approx 30 % of HIV associated PCP occur in people who are unaware of their HIV status  Risk is high- 1. previous bout of PCP 2.CD4 <200
  • 10. Clinical features-  Progressive dyspnea  Non productive cough  Characteristic retrosternal chest pain which is worse on inspiration(sharp or burning)  Fever  Unexpected weight loss
  • 11. Investigations  Sample- induced sputum (55%) and BAL(95%), transbronchial biopsy and open lung biopsy  CBC- mild leucocytosis  Elevated LDH  ABG- increase in arterial alveolar gradient  Recent- PCR has been used to detect specific DNA sequences
  • 12. Demonstration on tissue specimens Methanamine silver stained broncheoalveolar lavage (BAL) fluid Transbronchial lung biopsy stained with hematoxylin and eosin shows eosinophilic alveolar
  • 13. IMAGING Chest xray-  either a normal film or a faint perihilar interstitial infiltrate  Lobar infiltrates or pleural effusion less commonly CT-  patchy ground glass appearance
  • 15. PRIMARY AND SECONDARY PROPHYLAXIS
  • 16. Pulmonary tuberculosis  About 1/3 of death all AIDS related death associated with tuberculosis.  Tuberculosis is the primary cause of death in 10-12% HIV infection.  About 60-80% HIV infected patient With Tuberculosis have pulmonary disease, 30-40% have extra pulmonary involvement.
  • 17. Clinical features High CD4  Fever  Cough  Dyspnea on exertion  Weight loss  Night sweats Low CD4  Disseminated disease
  • 18. Comparison between PTB in HIV Vs Non HIV
  • 19. IMAGING  HIGH CD4 Cavitary apical lesion of upper lobes  LOW CD4 Diffuse and lower lobe bilateral reticulonodular infiltrates consistent with miliary spread, pleural effusions, hilar/mediastinal adenopathy
  • 20. Recommendations  Therapy of TB is generally same in the HIV infected person as in HIV negative patient.  Adjusted dose of Rifabutin are required when treating TB in the sitting of HIV  Initiation of ART and/or anti TB therapy may be associated with clinical deterioration due to IRIS  Initiation of ART delayed in antiretroviral naïve patients with CD4 above 50 until 2-4 weeks following treatment for TB  For patients <50 CD4 the benefits of ART outweigh the risks of ART
  • 21. IRIS  Immune reconstitution inflammatory syndrome.  Paradoxical worsening of an existing clinical condition or abrupt appearance of a new clinical finding (unmasking) is seen following initiation of ART.  Occurs 2 weeks to 2 years following the initiation of therapy.  CD4 count <50/microL who experience precipitous drop in viral load.  Reflects immediate improvement in immune function that occur as levels of HIV RNA drop and immunosuppressive effects of HIV are controlled.
  • 22. HISTOPLASMA  Histoplasmosis most commonly presents with disseminated disease in CD4 <150  Fever weight loss, adenopathy and mucosal lesions  It can also produce sepsis syndrome with hypotension and MODS  Presence of hilar or mediastinal lymphadenopathy may help as a distinguishing factor  Treatment – liposomal Amphotericin B Itraconazole
  • 23. Non infectious pulmonary complications KAPOSIS SARCOMA  Endothelial cells latently infected with HHV8 activated Angiogenesis leading to vascular malignancy  Pulmonary KS may be asymptomatic even in patients with extensive abnormalities on CXR  80% of patient with pulmonary KS have cutaneous lesions  Direct visualization of purplish plaques on bronchoscopy
  • 24.  Chest x ray bilateral pulmonary lower lobe infiltratesthat obscure margins of diaphragm and mediastinum  Pleural effusion in 70% cases of KS Treatment  Optimizaion of ART  Chemotherapy with doxorubicin, bleomycin and vinblastine
  • 25. HIV PAH  0.5 %  Shortness of breath, syncope, chest pain, signs of right heart failure and right sided cardiomyopathy  Most common hypothesis- alteration in pulmonary cytokine profile and increased expression of vasoactive substances like endothelin 1  Management- Prostaglandin agonist – epoprostenil Diuretics Sildenafil
  • 26. Aims and Objectives  1. To study pulmonary involvement in peoples living with HIV diagnosed by ELISA method.  2. To study radiological findings in lungs of PLHIV with pulmonary disease by chest x ray, High resonance computed tomography, ultrasonography of thorax etc.  3. To study co-relationship between CD4 count and pulmonary disease in PLHIV.
  • 27. Material and Methods Methodology  This is descriptive clinical study with cross sectional design with 100 HIV positive patients to study pulmonary involvement in people with HIV (PLHIV) patient. Source of Data  The study was conducted in Dr. V.M. Government Medical college, Solapur, Maharashtra, India, Present study was carried out on PLHIV with pulmonary involvement.  The period is from Dec.2012 to Nov. 2014. Present study was conducted after NACO permission
  • 28. Inclusion Criteria  1. Age>13 yrs  2. HIV positive patient diagnosed by ELISA method  3. Patient having pulmonary symptoms
  • 29. Exclusion Criteria  1. Age <13 yrs  2. HIV negative patient  3. PLHIV with only upper respiratory tract infection  4. PLHIV not willing to give consent
  • 30. Following investigations were done  1. Chest x ray PA view of all patients  2. Sputum for AFB -1 sample on admission, 2 sample on early morning  3. Sputum for gram staining  4. Sputum for pneumocystis jiroveci for GMS stain.  5. Sputum for culture and sensitivity  6. PAS Stain for mycobacterium avium complex
  • 31.  7. Pleural fluid study i.e. cyto, biochem or in suspected cases pleural fluid ADA  8. Ultrasonography of thorax in case of pleural effusion to rule out pulmonary involvement.  9. HRCT thorax in suspected patient in whom chest X-ray PA view is normal.  10. Fine needle aspiration cytology ( FNAC ) of lymph node in patient present with lymphadenopathy.  11. Blood culture, LFT, RFT, CBC, CD4 count in All patient.  12. ESR
  • 32. Observations and Results  71% were tuberculosis patient, followed by  22% were bacterial pneumonia patient followed by  7% were pneumocystis jirovecii pneumonia
  • 33. Disease wise distribution of study population DISEASE NO OF PATIENTS PERCENTAGE TUBERCULOSIS 71 71 PNEUMONIA 22 22 PCP 7 7 MAC 0 0 MALIGNANCY 0 0
  • 34. CXR PATTERN IN TB  Consolidations in 33.80% patient  Pleural effusion 23.94% patient  Fibro nodular infiltrate 16.90% patient  Cavitatory lesion in 16.90 % patient  Miliary tuberculosis in 14.08%,  Bilateral extensive tuberculosis 14.08%  Pneumothorax in 8% patient
  • 35. Chest X-ray findings in pulmonary tuberculosis patient CXR FINDING NO OF TB PATIENTS (%) CONSOLIDATION 24 (33.8%) PLEURAL EFFUSION 17 (24%) PNEUMOTHORAX 6 (8%) B/L EXTENSIVE TB 10 (14.1%) FIBRONODULAR INFILTRATE 12 (16.9%) MILIARY TB 10 (14.1%) CAVITATORY LESIONS 12 (16.9%)
  • 36. CXR PATTERN IN PNEUMOCYSTIS JIROVECI  95.5 % patient showed ground glass haziness on chest x ray out of which  33.33% patient had 1 zone involvement  66.66% patient had >1 zone involved  83.33% patient had lower zone involvement followed by  16.66% patient had upper zone  Parahilar Opacity in 71.42% patient
  • 37. Chest X-ray findings in Pneumocystis jirovecii pneumonia
  • 38. Co-relation between CD4 count and pulmonary disease CD4 count No. of bacterial pneumonia patient No. of tuberculosis patient No. of PJP patient >500 5 (22.76%) 1 (1.4%) 0 (0%) 201-500 9 (40.90%) 26 (36.61%) 0 (0%) 151-200 3 (13.63%) 14 (19.71%) 0 (0%) 101-150 10 (04.54%) 10 (14.08%) 1 (14%) 50-100 0 (0%) 12 (16.09%) 1 (14%) <50 4 (18.18%) 8 (11.26%) 5 (72%)
  • 39. Summary and Conclusion 1. In present study prevalence of tuberculosis was maximum in patient followed by bacterial pneumonia and pneumocystis jiroveci pneumonia respectively. 2. In present study prevalence of  Bacterial pneumonia was maximum in CD4 count >200cells/micro lit,  Tuberculosis was maximum in CD4 count between 150-500/micro lit,  Pneumocystis jiroveci pneumonia was max in CD4 count <50/micro lit.
  • 40. LIMITATIONS  Short duration of study.  Sample size was less i.e only 100 participants were considered for the study and the results of which could not be extrapolated to the general population.
  • 41. References  Harrison’s textbook of internal medicine, 20th edition.  API textbook of internal medicine, 11th edition.