HIV and LungsDr. Manjit S. TendolkarDept of Chest Medicine,

Seth G. S. Medical College & K. E. M. Hospital.

“HIV and Lung Diseases”

Significance

• Pulmonary complaints are often the sentinel event 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.

Introduction to HIV

• Single Stranded RNA

Virus

• Retroviridae Family

• Lentivirus Genus

• Two Species - HIV 1 &

HIV 2 (HIV 1 being more

common and more

virulent)

Respiratory Complains in HIV

• Bacterial Pneumonia- Typically acute

• Pneumocystis Pneumonia- Subacute to

Chronic, most prominent symptoms being

Fever an d Shortness of breath. Chest

Tightness.

• Fever, Night Sweats, Weight Loss ——

mycobacterial disease, fungal infection, or

non-infectious conditions such as non-

Hodgkin’s lymphoma

Past Medical History• History of opportunistic infections - Pneumocystis Pneumonia,

Tuberculosis, as there is a higher risk of recurrence.

• History of encapsulated bacterial infections like Streptococcus and H.

influenza, since some patients with HIV have more prominent B cell

dysfunction. — recurrent hospitalisations for bacterial pneumonia, as

well as episodes of otitis media, bronchitis, and other bacterial

respiratory infections.

• HIV-infected persons with active injection drug usage are more likely

to develop invasive bacterial infections, including pneumonia,

compared with HIV-positive individuals who acquired HIV from other

routes.

• Relative risk of pneumonia increases as CD4 count declines

Medication History

• Patients receiving trimethoprim sulfamethoxazole for

Pneumocystis prophylaxis rarely suffer breakthroughs of

PCP if they are compliant with therapy.

• Trimethoprim sulfamethoxazole has the added benefit of

reducing the risk of all bacterial infections, including

community pneumonia as well as less common HIV-

associated opportunistic infections such as nocardia and

toxoplasmosis. High rates of pneumococcal resistance to

trimethoprim sulfamethoxazole and macrolides must be

taken into consideration

Physical Examination• Alteration in mental status- Cryptococcus, as it can

produce both respiratory complains and meningitis.

• Auscultation of the lung fields is commonly normal in

diseases such as PCP but evidence of focal

consolidation can be a clue to bacterial pneumonia.

• prominent dermatologic findings include disseminated

fungal infections (cryptococcus and blastomycosis in

particular) and Kaposi’s sarcoma hepatosplenomegaly

or peripheral lymphadenopathy may be seen in

disseminated mycobacterial disease, fungal disease,

and non-Hodgkin’s lymphoma

Diagnostic Tests- In All Cases

• CBC- If neutropenia give empirical cover for Pseudomonas.

• LDH- Elevated in most cases of PCP, nonspecific.

• Blood Cultures- Bacterial Pneumonia, especially Streptococcus.

• Expectorated Sputum

• Induced sputum for PCP, AFB and Culture

If No Response to Empirical

Treatment

• Fiberoptic Bronchoscopy with BAL +/- Transbronchial Biopsy- since BAL is highly sensitive for PCP, Kaposis Sarcoma shows characteristic purple patch (NO BIOPSY- as risk of Bleeding), biopsy often necessary to establish alternative diagnosis such as CMV, aspergillus, or lymphocytic interstitial pneumonitis

• VAT Biopsy

• Serum Cryptococcal Antigen - 100% Sensitive. If positive CSF examination is mandatory to r/o meningitis.

• Urinary histoplasmosis antigen

• HRCT- If normal, PCP is unlikely

• Gallium Scan- If negative, rules out PCP. Positive test is non specific.

Specific Pathogens

Bacterial Pneumonias• Injection drug use more than doubles the risk of

bacterial lower respiratory track infections

compared with those who acquired HIV through

sexual exposure.

• Since encapsulated bacteria (in particular

Streptococcus. pneumoniae) are more intrinsically

virulent than the opportunistic infections of

advanced HIV disease, these infections may occur

at any stage of HIV disease and hence be the

sentinel opportunistic process in a person

otherwise unaware that he or she has HIV infection

• Neither the concomitant use of trimethoprim-

sulfamethoxazole for PCP prophylaxis nor a

history of having received immunization

against Streptococcus pneumoniae are

sufficiently protective against bacterial

pneumonia

• The most common identified pathogen in HIV-related

bacterial pneumonia is Streptococcus pneumoniae,

generally followed by Haemophilus influenzae

• Gram-negative bacilli and Staphylococcus aureus assume

increasing importance as immunosuppression worsens,

presumably due both to neutrophil dysfunction and

selective pressure of other antimicrobials

• Pseudomonas aeruginosa has been associated with

neutropenia, prior treatment with cephalosporins, and CD4

cell counts less than 50 cells/mm (Like individuals with

structural lung disease, pseudomonal respiratory infections

in HIV-infected patients have a tendency to relapse and

chronic colonization typically ensues, with relapse rates

after therapy between 25 and 86 percent.)

• MRSA pneumonia can be

quite severe and

commonly leads to

cavitation

• Pneumococcal vaccine is recommended for all

HIV patients who have a CD4 cell count

greater than 200 cells/mm3, and the influenza

vaccine should be given annually to all

patients, regardless of CD4 cell count

Pneumocystis jiroveci

• PCP in patients with HIV infection usually presents subacutely with progressive dyspnea,

non-productive cough, and fever. Pleuritic chest pain or acute worsening of symptoms is an

unusual manifestation of PCP in patients with HIV unless complicated by the development of

a pneumothorax.

• lungs are generally clear on auscultation.

• Diagnosis: Induced sputum - 55% sensitivity

BAL - 95% sensitivity

• Persistence of organisms through and even after therapy is common, and does not reflect

failure of therapy.

• Newer diagnostic techniques under investigation include polymerase chain reaction of saliva

or sputum, as well as blood tests measuring levels of S-adenosylmethionine, a metabolite

used exclusively by Pneumocystis jiroveci and hence lowered in patients with active disease.

• Chest imaging may be normal but more typically demonstrates bilateral diffuse interstitial

abnormalities

• Patients with PCP typically worsen after 2 to 3 days of therapy.

Endemic Fungi

• Histoplasmosis, coccidioidomycosis,

blastomycosis, and penicilliosis are dimorphic

fungi that are endemic to distinct regions but

that may reactivate

• rarely causes disease in patients with HIV until

the patient is significantly immunosuppressed

(CD4 less than 250 cells/mm3).

Histoplasma capsulatum

• histoplasmosis most commonly presents with disseminated disease in an individual with a CD4 cell count less than 150 cells/mm3.

• fever, weight loss, adenopathy, diarrhea, andmucosal lesions.

• occasionally occurs in person with HIV and preserved CD4 counts (greater than 350 cells/mm3)

• Histoplasma capsulatum can produce a sepsis syndrome as well with fever, hypotension, and multiorgan system failure.

• The presence of hilar or mediastinal adenopathy may help distinguish histoplasmosis from Pneumocystis jiroveci, as the clinical presentation in susceptible hosts overlap significantly, although these are uncommon findings for Pneumocystis.

• Diagnosis: detection of polysaccharide antigen in urine or blood, where urine testing has been shown to be positive in up to 95 percent of patients with disseminated disease and AIDS.

• Treatment: Amphotericin is currently considered the drug of choice for severe or disseminated histoplasmosis in HIV-positive patients and should be continued for 3 to 10 days until clear clinical improvement has occurred before patients are switched to itraconazole to complete a total of 3 months of therapy. Patients with HIV infection be maintained on suppressive doses of itraconazole indefinitely.

Coccidioides immitis

• The presence of hilar adenopathy, eosinophilia, or lack of response to conventional antibiotics should prompt consideration of pulmonary coccidiomycosis in patients from endemic areas

• Radiology: diverse, and may include reticulonodular disease, alveolar infiltrates, nodules, adenopathy, cavities, and pleural effusions.

• Diagnosis: Iolation in respiratory secretions (Bronchoscopy)

• Coccidioides immitis serology has a more established role to play in monitoring response to therapy. (sensitivity in diagnosis is 70%)

• DOC: (Without meningeal involvement) Amphotericin B. Treatment should be continued until clear clinical improvement has been demonstrated, at which time patients may be switched over to itraconazole or fluconazole.

• (With meningeal involvement): high-dose fluconazole, therapy should be continued indefinitely.

Penicillium marneffi

• Penicillium marneffei is generally seen in patients with advanced AIDS(CD4 less than 50 cell/mm3), where it commonly presentswith extrapulmonary symptoms (fevers, weight loss, sweats, hepatosplenomegaly, and hematologic abnormalities).

• cutaneous findings, particularly umbilical papules that may be confused with either cryptococcosis or molluscum contagiosum

• much more commonly associated with systemic disease, then isolated pneumonia.

• Chest radiographs most demonstrate interstitial changes though nodules, cavitation and pleural disease have all been reported previously.

• diagnosis requires isolation of the organism from blood, skin,bonemarrow, or lymphnodes.

• In patients with disseminated infection, amphotericin B should be used to control the infection. Patients who have demonstrated clear clinical improvement can be switched to twice-daily itraconazole to complete a 3- month treatment course. secondary prophylaxis with daily itraconazole should be maintained until patients have achieved a CD4 count of greater than 200 cells/mm3 for at least 6 months.

• Fluconazole does not have activity against Penicillium marneffei.

Aspergillosis• exclusively in those with advanced immunosuppression(CD4 cell

count less than 50 cells/mm3.

• Patients with AIDS who are diagnosed with invasive disease often

have other risk factors for aspergillosis, such as receipt of

corticosteroids or neutropenia.

• Aspergillus fumigatus, and to a lesser extent Aspergillus niger are the

most common causes of invasive aspergillosis.

• Respiratory tract disease is the most common manifestation of

aspergillosis and both tracheitis and invasive pneumonitis may

develop

• The diagnosis is established when endoscopic examination reveals

an exudative pseudomembrane adherent to the tracheal wall.

• Radiographic abnormalities in both of these forms

overlap, and can show diffuse infiltrates, cavities,

and focal wedge-shaped abnormalities reflecting

pulmonary infarction.

• Despite the predilection for the organism to invade

blood vessel walls and disseminate, focal CNS

disease due to aspergillus in AIDS patients

appears to arise more commonly from contiguous

spread from the sinuses, orbits, and ears.

• It is important to note, however, that aspergillus is

a common colonizer of diseased airways, so

definitive diagnosis requires documentation of

tissue invasion

• Voriconazole as the agent of choice for invasive

aspergillosis, although potential drug-drug

interactions in patients receiving antiretroviral

medications should be closely monitored.

• There are no formal recommendations for length

of treatment or prophylaxis (secondary or

primary), although every effort should be made

to provide effective antiretroviral therapy, to

correct neutropenia by discontinuing offending

agents or by using stimulatory cytokines, and to

eliminate exogenous immunosuppression by

discontinuing corticosteroids.

Viral Pneumonia

• Although many respiratory viruses produce

disease in patients with HIV, only

cytomegalovirus is an AIDS-defining

opportunistic infection

Cytomegalovirus• Asymptomatic persons with CMV infection excrete the virus in

saliva, respiratory secretions, urine, and semen.

• Clinically significant HIV-related CMV infection is associated with

severe immunosuppression (CD4 less than 50 cells/mm3).

• CMV-associated syndromes most commonly seen in patients with

AIDS are retinitis and enteritis (colitis or esophagitis).

• A variety of CMV-related neurologic complications have been

described, including polyradiculitis, ventriculitis, and mononeuritis

multiplex.

• When disease is limited to the chest, definitive diagnosis requires

demonstration of cytopathic change on histopathology (usually

obtained via transbronchial biopsy or VATS).

• In most studies, patients with positive BAL

cultures for CMV have evidence of a more

likely alternative diagnosis (especially PCP or

bacterial pneumonia), and may improve

2without specific therapy directed at CMV.

• Nonetheless, in a patient with advanced HIV

disease (CD4 cell count less than 50

cells/mm3), interstitial infiltrates on chest

radiograph, and no alternative organism

isolated, CMV pneumonitis may be the sole

responsible pathogen.

• The agents of choice for the treatment of

established CMV pneumonitis is oral

valganciclovir.

• For refractory disease, foscarnet would be an

appropriate alternative, although its use is

associated with high rates of renal dysfunction

and other metabolic abnormalities.

• Unlike CMV retinitis, there is no standard

secondary prophylaxis for CMV pneumonitis.

However, as with other opportunistic infections,

the antiretroviral therapy with restoration of the

CD4 cell count plays a critical role in preventing

recurrences.

• all patients with HIV infection should be

encouraged to get annual vaccination.

Although declines in CD4 count and rises in

HIV viral load may be seen after influenza

vaccination, these adverse laboratory events

are generally transient and have not been

shown to be associated with adverse clinical

events

Parasitic Infections• Toxoplasma gondii most common.

• CD4 less than 50 cells/mm3.

• The clinical presentation of pulmonary toxoplasmosis is similar to that of PCP, but

unlike PCP it may be accompanied by a sepsis-like syndrome with hypotension.

• Radiographic abnormalities are diverse- interstitial infiltrates, but also potentially

nodules, effusions, or mass lesions.

• As with PCP, an elevated LDH is a commonly reported laboratory finding. Diagnosis

may be established by identification of toxoplasma tachyzoites on Giemsa stain of BAL

fluid or tissue obtained on biopsy.

• Treatment- Pyrimethamine plus sulfadiazine is the first-line treatment x 6 weeks, and

secondary prophylaxis until their CD4 count is greater than 200 cell/mm3 for over 6

months.

• Prophylaxis with double strength TMP/SMX once daily in HIV-positive patients with

CD4 counts less than 100 cell/mm3

Non Infectious Pulmonary

Complications of HIV

Kaposis Sarcoma• Endothelial cells latently infected with HHV8 are activated by HIV, which in turn

drive the angiogenesis characteristic of this vascular malignancy

• KS may develop in patients with preserved CD4 counts, although the pulmonary

involvement is most commonly seen in advanced disease (CD4 less than 100

cells/mm3

• Pulmonary KS may be asymptomatic even in patients with extensive

abnormalities on chest radiograph.

• Lesions tend to show peribronchovascular distribution

• Diagnosis is generally made through direct visualisation of characteristic purplish

plaques on bronchoscopy

• Chemotherapy is indicated for symptomatic pulmonary disease

• However, as with cutaneous KS, potent antiretroviral therapy can induce

significant improvement in pulmonary KS, as well as sustained remissions.

Lung Cancer

• Lung cancer is the most frequently diagnosed

non-AIDS–related malignancy, with reported

rates of three- to eightfold higher than those

without identified infection

• While CD4 count at the time of diagnosis of

lung cancer may be depressed, it is more

commonly preserved.

Pulmonary Hypertension

• The most common hypothesis for the association of HIV and

pulmonary HTN is an alteration in pulmonary cytokine profile that

increases expression of vasoactive substances such as endothelin-1

• HIV-related pulmonary hypertension (HRPH) is a diagnosis of

exclusion and can only be made after other secondary causes of

pulmonary hypertension have been excluded.

• Management of pulmonary hypertension is as for HIV-negative hosts,

with prostaglandin agonists (epoprostenol), diuretics, and

anticoagulation. Sildenafil may also have a role, but it is associated

with potential drug-drug interactions in patients receiving with

protease inhibitors

• reports have not shown a consistent beneficial response of this

condition to antiretroviral therapy.

Lymphocytic Interstitial

Pneumonia• More commonly in HIV-infected children, adults may

rarely develop this complication as well. LIP is

characterised by polyclonal inflammatory lymphoid

proliferation of bronchus associated lymphoid tissue

(BALT).

• Diffuse reticulonodular or interstitial infiltrates are seen

on chest imaging, making differentiation from PCP

difficult

• Several case reports have demonstrated that

antiretroviral therapy may lead to substantial

improvement in LIP

• For unresponsive cases, corticosteroids may be

effective.

COPD

• greater risk for the development of

emphysema

• Investigators have postulated that the higher

proportion of CD8+ T lymphocytes seen in

BAL fluid from patients with HIV compared

with uninfected controls may help explain this

difference.

Thromboembolism

• Patients with HIV infection are at two- to

tenfold increased risk of thromboembolic

disease

Abacavir Hypersensitivity

• 5% individuals

• Symptoms of the abacavir HSR usually appear in the first 6 weeks of

treatment and include fever, rash, malaise, GI upset, myalgia, and

arthralgias. Cough and dyspnea also may occur and may mimic

bronchitis or pneumonia.

• It is critical that clinicians evaluating patients who have recently been

started on abacavir who present with fever and respiratory symptoms

consider abacavir hypersensitivity in the differential diagnosis, as

continued abacavir treatment in the face of this reaction can be fatal

• Symptoms resolve after cessation of drug.

• Never resume abacavir, as there might be immediate and life

threatening recurrence of hypersensitivity

Thank You