Pulmo complications in HIV

1. PULMONARY COMPLICATIONS IN
IMMUNOCOMPROMISED PATIENTS
(HIV)
Dr.Amara Nadeem

2. • Pulmonary complaints are often the sentinel events that leads to
the diagnosis of HIV infection in persons who are unaware of their
HIV status
• Respiratory complications remain a common cause of adverse
outcomes in HIV infected individuals

3. • Single stranded RNA virus
• Retroviridae Family
• Replication in human lymphocytes (CD4+T-cells)
• Two species (HIV 1 & HIV 2)
• HIV 1 – more common & virulent

4. Susceptibility to infections in HIV
Infections with HIV – viral replication in pool of helper T lympho (CD4) – depleting nos &
ability to function
Reduced cell-mediated immunity – reduces humoral immune functions
Best available marker for immune function – CD4 lymphocyte count
<200 cells/µL – moderate immunosuppression
<100 cells/µL – severe immunosuppression

6. • Tuberculosis
• Kaposi Sarcoma
• CD4 count ~500 cells/µL
• PCP
• CD4 count ~200 cells/µL
• Disseminated MAC infection
• CD4 count ~100 cells/µL

7. HAART (Highly Active Antiretroviral
Therapy)
• Used in combinations – suppress HIV replication – profound impact
• Inc life expectancy
• Early start – regardless of CD4 count
• START trials:
• Immediate treatment associated with
• 50% dec in risk for severe illness or death
• Compared to wait for CD4 count to fall <350 cells/µL

8. After decision is made
• Several guidelines for therapy
• AS RESISTANCE DEVOLOPS AGAINST ART
• GOAL should be : complete suppression of viral load
• Thus COMBINATION THERAPY :
• At least 3 medications
• From at least 2 different groups
• NOTE
• 2 drug regimes inc PROTEASE INHIBITORS – under study
• Partial Suppressive Combinations
• Eg; Dual Nucleoside Therapy – avoided
• When Toxicity develops
• Change offending medication
• Rather than reducing individual doses

9. CLASSIFICATION OF ART
• Abacavir, Didanosine, Emtricitabine, Stavudine, Zidovudine
Nucleosides Reverse Transcriptase
Inhibitors
• Tenofovir
Nucleotide Reverse Transcriptase
Inhibitors
• Delavirdine, Efavirenz, Navirapine
Non-Nucleoside Reverse Transcriptase
Inhibitors
• Saquinavir, Indinavir, Nelfinavir, Amprenavir, Ritonavir etc
Protease Inhibitors
• Enfuvirtide
Entry Inhibitors
• Dolutegravir, Raltegravir
Integrase Inhibitors

10. Effect of
HAART on
Respiratory
Complications
• Successful use of Combinations – suppression of
HIV replication & restoration of immune functions
• Remarkable decline in Pulmonary Complications
eg; PCP, TB & Bacterial Pneumonia
• Exceptions : Non Compliance
Non Effectivity

11. Most Common Bacterial Respiratory Infections
Regardless of severity of
immunosuppression
• Most Common
• Bacterial Bronchitis
• Pneumonia
• May be recurrent
• Esp in patients with severe
immunosuppression
Incidence of Bacterial
Pneumonia is highest among
• Severe immunosuppression
• Injection Drug users
• CD4 count <200 cells/µL

12. BACTERIAL PNEUMONIA
presentation
Similar in with or
without HIV
Although bacteremia is
more common with HIV
Rapid onset (hours to
days)
Fever, productive
cough, dyspnea, chest
pain
Leukocytosis is
common
LDH usually normal or
slightly elevated
CX-Ray
•Segmental/lobar infiltrates
•Diffuse pattern may be seen
(H.Influenza)
•Cavitation may occur (Staph
aureus, P. auregenosa)

13. Role of CT scan
in diagnosis of
Bacterial
Pneumonia
• CX-Ray findings are typical
• & culture/serology failed to identify
organism
Useful when
• Better on CT than other conventional
radiographs
Nodules, Cavities & fluid
collection
• Empyema
• abscess
Also better in diagnosing and
managing complications

14. NECROTIZING CAVITATING
PNEUMONIA Chest X-ray and
computed tomography depicting
necrotizing cavitating
pneumonia due
to Staphylococcus aureus in a
29-year-old male with acquired
immunodeficiency syndrome

15. Causative Organisms of Bacterial Pneumonia
in HIV patients
• Strep Pneumonia & H. Influenza
• Most Common
• So initial empirical treatment directed against them
• Mycoplasma Pneumonia & Chlamydia Pneumonia
• Common in general population
• Unusual in patients with HIV
• P. Aeruginosa
• May cause CAP or HAP
• Usually when CD4 <50 cells/µL

16. Treatment
• Antibiotics
• 3rd Gen Cephalosporin (ceftriaxone &
Cefotaxime)
or
• A newer quinolone (Levo & Gati)
GIVEN AS INITIAL EMPIRICAL THERAPY
May be changed after
• Culture reports
• Non responding treatment
• TMP-SMZ (Septran) is drug of choice in PCP

17. PNEUMOCYSTIS
PNEUMONIA (PCP)

18. Definition
• Clinical syndrome of pneumonia
from inf. with PNEUMOCYSTIS
JEROVECCI
• Widespread in environment
• Infection by age 2 years
• Person-person transmission

19. Risk Factors
HIV infection (CD4
<200 cells/µL)
Chemotherapy
Treatment (esp.
Fludarabine)
Corticosteroids or
other
immunosuppressants
Malnutrition in
children
PCP occurring in AIDS
associated with
• Greater no of organisms
• Fewer inflammatory cells
in lungs
Compared to
infections with other
causes of
immunocompromised

20. • Prophylactic Co-Trimoxazole
• Post transplantation
• ALTHOUGH CASES STILL MAY OCCUR
Less common in patients
• Still unclear
• Dose equivalent to 16mg prednisolone or greater for 8 weeks increases the
risk
Steroid Predisposition to PCP

21. Clinical
Features
Gradual Onset
of
• Dry Cough
• Exertional SOB
Sometimes
retrosternal
Chest tightness
Fever,
Tachypnea
Chest exam
typically normal
May present
with
pneumothorax
Extra
pulmonary -
Rare

22. Investigation
• B/L perihilar Infiltrates
progressed to alveolar shadowing
• Less commonly
• Small nodular infiltrates
• Focal consolidation
• CX-Ray normal in about 10%
• Pleural effusion Rare
CX-Ray
• Except in cases of normal CX-Rays
where it may present as ground
Glass pattern & Cystic Shadowing
CT
routinely
not
required

23. If left untreated, chest X-ray may progress to alveolar
consolidation in 3 or 4 days. Infiltrates clear within 2
weeks, but in a proportion, infection will be followed
by coarse reticular opacification and fibrosis. Note the
large cyst (arrow)
PNEUMOCYSTIC
PNEUMONIA

24. HRCT showing the hallmark of PCP in a
clinical setting of immune compromise.
Note the ground-glass attenuation with
a geographic or mosaic distribution
PNEUMOCYSTIS PNEUMONIA

25. Lung cysts are usually multiple and
bilateral, but range in size, shape and
distribution. They are more commonly
appreciated on computed tomography
(CT)/high-resolution CT
PNEUMOCYSTIS PNEUMONIA

26. Investigation
• Common
• Desaturation with exercise and normal at rest
• Suggests the diagnosis
Hypoxia
• Usually Normal
• Serum LDH usually raised (sensitive but not
specific)
WBCs
• Diagnostic yield of 60% in HIV
• Much less in non HIV immunocompromised
due to lower organism burden
Induced Sputum

27. Investigation
• Bronchoscopy with BAL
• Diagnostic Investigation Of choice
• In non HIV
• In HIV where induced sputum is not
diagnostic
• BAL with Silver or Immunoflorescent staining
• Specificity 100%
• Sensitivity 80-90%
Sensitivity dec in non HIV due to dec pathogen
load

28. Investigation
Trans Bronchial Biopsy
• Slightly higher sensitivity –
95%
• Associated with inc risk of
complications
• Reserved for cases where
BAL is not diagnostic
Surgical Lung Biopsy
• May be needed for
diagnosis in minority of HIV
neg patients

29. Treatment
• Anti-Microbials
• Consult with Infectious disease center & HIV
specialists
• High Dose CO-TRIMOXAZOLE – Drug Of Choice
• 120mg/kg daily in 4 divided doses – PO
or
• IV (dilute 480mg amp in 75 ml 5% Dextrose inf
over 60 min)
INITIALLY IV then PO with clinical improvements
• Second Line Choice
• If intolerant or unresponsive to Septran
• IV Pentamidine (3-4 mg/kg IV daily)
• Clindamycin & Primaquine (600mg IV/PO TDS)
• Dapson & Trimethoprim (100mg PO daily/5-
6mg/kg PO TDS)
• Atovaquone (750 mg BD)

30. Treatment
• All treatments should be for 2-3 weeks
• In cases of HIV presenting with PCP
• Early introduction of HAART is controversial
• Due to theoretical risks of drug interactions
• Increasing toxicities
• Potential for IRIS
• Randomized trials & retrospective analysis
• Demonstrates 50% dec in mortality when starts within 2 weeks of PCP therapy
NOTE: suspected IRIS should be countered with corticosteroids ± reintroduction
of PCP therapy

31. • Steroids
• High dose Steroids
• Prednisolone 40mg BD PO
Or
• IV Hydrocortisone
Recommended in all patients with Resp Failure
Treat at High Dose for 5 Days
Taper dose over 1-3 week
eg; Prednisolone 40mg daily for days 6-11, then daily 20mg for
days 12-21
Treatment

32. Treatment
• Supportive Therapy
• Hypoxia
• Supplimentary High Flow O2
• Use of CPAP
• Mechanical Ventilation

33. Outcome
Mortality
• 10-20% in AIDS
• 35-50% in other forms of immunocompromised
• Reflecting the adverse consequences of greater
pulmonary response to pneumocystis observed in
non HIV immunocompromise
• Mortality – 60% in PCP with HIV patients requiring
mechanical ventilation
• May be significantly Higher in Patients with lower
CD4 count
Relapse Rate in AIDS
• High(60% in 1 year) so 2o prophylaxis with Co-
Trimoxazole – recommended
• 1o prophylaxis needed in HIV patients with CD4
count <200 x 106 L
• Consider prophylaxis in patients receiving high dose
steroids for prolonged periods

34. TUBERCULOSIS
in HIV patients

35. Regimes are same (standard 4
drugs)
Identification of HIV – need special
care to be added
> Co-trimoxazol prophylaxis
> Early ART – improves mortality HENCE HIV TESTING IN ALL TB
PATIENTS IS IMPORTANT
Newly diagnosed cases – start ATT
before HIV – ART started within first
8 weeks of ATT (CD4 counts <50 x
106/L – start ART within 2 weeks)
• Exception is TB meningitis – avoid early ART
Protease Inhibitors – not be used
with RIFAMPICIN (interference with
metabolism)
Paradoxical worsening of symptoms
(worsened fever, CXR infiltrates, inc
lymphadenopathy etc) at initiation
is common (˜15%) – so-called TB-IRIS
– shows pathogens-specific immune
responses
• Steroids reduce the morbidity associated with
IRIS

36. Death during ATT – more common in HIV
Higher relapse rates
• With CD4 <200 x 106/L
• Disseminated TB with multi organ involvement
• Mycobactremia
• Sparing of Lung occur in CD4 <75 x 106/L
Atypical presentations of TB – common
Active TB may be asymptomatic in HIV patients

37. Chest X-ray and computed tomography
showing features of
reactivation Mycobacterium
tuberculosis as patchy consolidation,
including involvement at unusual sites,
e.g. lower lobes as seen here,
cavitation, nodularity and adenopathy

38. “Primary” Mycobacterium
tuberculosis. Chest X-ray shows
right upper lobe and left midzone
consolidation and adenopathy.
Note lack of cavitation in this
patient with a low CD4 count

39. MAC
(Mycobacterium
Avium Complex)
M. Avium
M. Intracellulare
Infection with MAC can occur in HIV & non-HIV
Principal Forms of MAC in HIV
Disseminated Disease
Focal Lymphadenitis
isolated pulmonary infection is typically seen in immunocompetent
patients.

40. Among HIV – MAC – CD4 Count <50 cells/µL
• With use of prophylaxis against MAC early in epidemic
• Widespread use of effective ART
Dramatic Declines in MAC
• Inhalation
• Ingestion
• Inoculation
Transmission

41. MAC
EPIDIMIOLOGY
• Risk increases as CD4 count declines <50 cells/µL
• Incidence of disseminated MAC - 20% to 40% (with
severe AIDS-associated immunosuppression - in the
absence of effective ART
• Overall incidence of disseminated MAC among
HIV-infected patients - fallen more than 10-
fold - since the introduction of effective ART
• Other Factors
• High plasma HIV RNA levels (>100,000
copies/mL)
• previous OIs
• previous colonization of the respiratory or
gastrointestinal tract with MAC

42. MAC
Clinical Manifestations
Not on ART – Disseminated MAC (multi
organ disease)
• Detectable mycobactremia
• Symptoms : fever, weight loss, fatigue,
diarrhea, abdominal pain
On ART – Local manifestations – inc CD4
count – improved immune response
• Localized symptoms
• Cervical & Mediastinal Lymphadenitis,
pneumonitis, pericarditis,
osteomyelitis, genital ulcers etc
• May be due to IRIS
• Clinical manifestions of IRIS – same as
in TB-IRIS
• Bactremia – absent

43. MAC
Diagnosis
• Compatible clinical signs
• Coupled by Isolation of MAC from
cultures
• Of blood, LN, bone marrow,
Confirmed diagnosis by
• AFB smear
• Radiographic imaging
• Isolating organisms from focal
sites
Supportive diagnostic
features

44. MAC
Prevention
• Should receive chemoprophylaxis against MAC
• If CD4 count <50 cells/µL
Indications for Primary Prophylaxis
Azithromycin & Clarithromycin – preferred drugs
Rifabutin – Alternative drug
• Clarithro + Rifa - ↑ S/E – SHOULD NOT BE USED
• Azithro + Rifa - Not recommended
Combinations Studies

45. • If intolerant to Azithro or Clarithro – Rifabutin
• Before prophylaxis – MAC should be confirmed – via blood cultures
• Before Rifabutin-based prophylaxis – TB should rule out – causing acquired
resistance to MTB in active TB
• Discontinuation Of Prophylaxis
• When patient responded to ART – inc in CD4 count (>100 cells/µL) – for ≥3
months
(2 randomized, placebo controlled trials &
observational data)
• Primary prophylaxis should be REINTRODUCED when CD4 count falls <50 cells/µL

46. MAC
Treatment
Initially treat with 2 or more
antimicrobials to delay or prevent
resistance
CLARITHROMYCIN/AZITHROMYCIN –
First line
ETHAMBUTOL – Second Line
RIFABUTIN – Third in choice
Amikacin/Streptomycin or
Levo/Moxi
NOTE: add 3rd or 4th drugs if
•Advanced immunosuppression (<50 cells/µL)
•High mycobacterial load
•Absence of effective ART

47. Special
Consideration
to start ART
• Start ART as soon as possible after 2 weeks – after
starting antimicrobial therapy – either with
previous Hx of ART or not
• Start Antimicrobial early to dec pill
burden & reduce risk of drug
interaction
• Significance of starting ART as soon as
after 2 weeks is to prevent from
further OIs & improve response to
antimicrobial therapy in
immunocompromised state
• Need continuous antimicrobial therapy until
achieving immune reconstitution via ART

48. Monitoring of Response to Therapy & Adverse
Effects (inc IRIS)
• Improvement in fever & dec quantity of mycobacteria – expected in 2-4 weeks
after initiation of therapy
Repeat blood culture for MAC – 4-8 weeks after antimicrobial
therapy – only in patients with failure to response
• Then initially start NSAIDS
• If not improved then short term (4-8 weeks) – systemic corticosteroids
• prednisolone 20-40mg/daily helps reducing symptoms & morbidity
Person having symptoms like IRIS during ART

49. KAPOSI
SARCOMA
HHV-8 (also known as Kaposi
Sarcoma Herpesvirus)
Most common malignancy
related to AIDS
Usually affects skin (typical
Violaceous or Red Plaques)

50. KAPOSI
SARCOMA
Clinical
Presentation
Usually have skin disease
Often no pulmonary symptoms
• Chronic cough
• Hemoptysis
• Infection related to bronchial
obstruction
• Dyspnea with extensive parenchymal
involvement
• Or Large Pleural Effusion
• Weight Loss & Fever also common
Most Common Complaints

51. Skin
Involvement
in KS
Usually have cutaneous
manifestations
Important clinical clue
However 15% - no
cutaneous involvement
Oropharyngeal lesions –
also common

52. KAPOSI
SARCOMA
Radiological
Findings
Linear Opacities following
septal lines (Kerley’s B
Lines)
• Ill defined
• Various sizes
Nodular Opacities
• May be unilateral
• Or Bilateral
Pleural Effusion
Hilar/Mediastinal
Lymphadenopathy
Bronchial Thickening
NOTE: HRCT – useful in
diagnosis in patients with
indistinct findings on
standard radiographs

53. Kaposi’s sarcoma is the
most common acquired
immunodeficiency
syndrome-related
malignancy. The chest X-
ray shows bilateral
perihilar/lower zone
reticulonodular
infiltrates

54. KAPOSI SARCOMA. Pleural
effusions chest X-
ray/computed tomography
are common. They may be
unilateral or bilateral and
may be large and
characteristically
hemorrhagic on aspiration

55. KAPOSI
SARCOMA
Diagnosis
Usually inferred by
visualizing typical lesions
in PHARYNX or the
TRACHEOBRONCHIAL tree
Cytology of sputum BAL
fluid – rarely diagnostic
• Because endobronchial lesions are
deep below the mucosa
• And parenchymal lesions are patchy
Histological diagnosis of
bronchoscopic lung Biopsy
specimens - low
diagnostic yield (26-60%)
Pleural Fluid cytology &
Pleural Biopsy – rarely
helpful
• But rarely performed
• Because bronchoscopy is adequate to
visualize airway lesions to rule out inf
OPEN LUNG BIOPSY HAS
HIGHEST YIELD

56. Kaposi’s sarcoma. High-resolution computed
tomography shows thickening of the
bronchovascular bundles reflecting
bronchocentric disease. Interlobular septal
thickening due to lymphatic obstruction
because of tumor invasion is also seen

57. KAPOSI
SARCOMA
Treatment
• Depends upon site
• And extent of involvement
Must be individualized
• Cytotoxic chemotherapy
• Vinca Alkaloids
• Etoposides
• Bleomycin
• Liposomal Anthracyclines, Paclitaxel,
angiogenesis inhibitors, thalidomide,
Interferon Alpha, retinoic acids
• All been used
Patients with disseminated
disease

58. KAPOSI
SARCOMA
Effect of HAART
on prognosis
Most promising approach – use of HAART –
Regression of KS lesions
PROTEASE INHIBITOR-based & NON-
NUCLEOSIDE REVERSE TRANSCRIPTASE
INHIBITOR-based – undetectable KSHV load
ass with KS regression
•Blocks
•angiogenesis
•KS lesion formation
•Tumor Growth
PROTEASE INHIBITOR

59. IRIS (Immune
Reconstitution
Inflammatory
Syndrom)
• Paradoxical Deterioration in clinical status
attributable to the recovery of immune system
during HAART
• Diagnostic Criteria
• Dx of AIDS
• Current HIV treatment
• Symptoms consistent with an infectious or
inflammatory condition that appeared while
on ART
• Symptoms that cannot be explained by newly
acquired infection, by expected clinical course
of disease or by side effects of therapy

60. IRIS
Association
with Diseases
• Mycobacterium Tuberculosis
• PCP
• KS etc
Cases of paradoxical deterioration
after initiation of HAART
• Patient may develop
• Fever
• Pulmonary Infiltrates
• Thoracic Lymphadenopathy
• Pleural effusions
TB-IRIS
PCP : HAART may lead to
deterioration & Resp Failure

61. IRIS
Diagnosis
• Compatible clinical syndrome in patient
• Recovering from infection
• Being treated by HAART
• Plasma HIV load – improves
• CD4 count improves compared to prior
measurements
• Opportunistic infections – diagnostic
consideration
IRIS is diagnosis of Exclusion
• In patients with likely to be IRIS
• & non life threatening symptoms
Invasive procedures – avoided

62. IRIS
Treatment
• Eg; Antipyretics for Fever
etc
Patient already on
symptomatic therapy
• Used for severe
inflammatory disease
• And End Organ Failure
Systemic
Corticosteroids