What’s new?

C In populations with access to combination antiretroviral ther-

apy (cART) there has been a marked reduction in the incidence

HIV/AIDS BY SYSTEM

HIV and the lungJamilah Meghji

Robert F Miller

of many HIV-associated infectious and malignant pulmonary

diseases

C Immune reconstitution inflammatory syndrome (IRIS) is more

widely recognized as a cause of paradoxical disease exacer-

bation on initiation of cART

C Despite cART, bacterial pulmonary infections continue to be

more common in HIV-infected individuals than in the general

population

C Non-infectious respiratory complications of HIV, such as chronic

obstructive airways disease and lung cancer, are increasingly

recognized in an ageing population

AbstractRespiratory disease remains a common cause of morbidity and mortality

in HIV-infected patients. The spectrum of disease is broad and includes

infection, malignancy, airway, parenchymal, pleural, and vascular pathol-

ogy. The pattern of disease has changed markedly in populations where

combination antiretroviral therapy (cART) is available; the incidence of

many opportunistic infections and malignancies has fallen, although

rates remain higher than in the general population, and conditions such

as chronic obstructive pulmonary disease and lung cancer are increasing

as life expectancies rise. Controversies still remain over the timing of cART

in relation to the treatment of opportunistic infections such as tubercu-

losis, and the diagnosis and treatment of the immune reconstitution in-

flammatory syndrome (IRIS).

Keywords AIDS; antiretroviral therapy; bacterial pneumonia; COPD; HIV

infection; pneumonia; pneumocystis pneumonia; prophylaxis

Introduction

Despite the widespread use of combination antiretroviral therapy

(cART) respiratory disease remains a common cause of morbidity

and mortality among HIV-infected adults; most will experience at

least one significant respiratory illness during their lifetime

(Table 1). With cART the incidence of many opportunistic in-

fections, including Pneumocystis jirovecii pneumonia (PCP),

cytomegalovirus disease and Mycobacterium avium complex, and

some malignancies, including Kaposi’s sarcoma, has fallen

significantly. cART has had less impact on the incidence of bac-

terial pneumonia, tuberculosis (TB) and non-Hodgkin’s lym-

phoma. As patients are living longer, non-malignant chronic lung

disease is increasingly encountered.1

Infection

HIV directly impairs innate and adaptive immune responses

leaving the respiratory tract vulnerable to infection. Treatment

with cART does not fully restore immune function.2

Jamilah Meghji MBBS MRCP MPH is a Specialist Trainee in Respiratory

Medicine in the North West Thames Region, London, UK. Her research

interest lies in respiratory epidemiology. Competing interests: none

declared.

Robert F Miller MBBS FRCP is Reader in Clinical Infection at University

College London Medical School, University College London, London,

and Honorary Professor at the London School of Hygiene and Tropical

Medicine, UK. His research interests relate to the effects of HIV on

innate immunity and the respiratory complications of HIV infection,

particularly Pneumocystis jirovecii pneumonia and tuberculosis.

Competing interests: none declared.

MEDICINE 41:8 435

Bacterial infections

Upper respiratory tract infections, acute bronchitis and acute

sinusitis occur more commonly in HIV-infected patients than in

the general population. Symptomatic chronic sinusitis affects

more than 15% of HIV-infected individuals, particularly those

with CD4 counts less than 200/ml (normal count is 470e1450/ml).

Bronchiectasis: bronchiectasis is increasingly recognized among

HIV-infected adults. It is probably due to recurrent bacterial,

mycobacterial and P. jirovecii infections. Management is as for

adults bronchiectasis unassociated with cystic fibrosis. Among

those with vertically acquired HIV infection who survive to late

adolescence/early childhood (with or without cART), bronchi-

ectasis probably occurs secondary to lymphocytic interstitial

pneumonitis or to obliterative bronchiolitis.

Bacterial pneumonia: the incidence of community-acquired

bacterial pneumonia remains high in HIV-infected patients,

although reduced by cART. Injecting drug users, cigarette

smokers, and those with low CD4 counts are particularly at risk.

Presentation is similar to that in the HIV-uninfected population.

Commonly isolated pathogens are Streptococcus pneumoniae and

Haemophilus influenzae. Staphylococcus aureus and Gram-

negative organisms such as Pseudomonas aeruginosa are seen

in advanced disease (CD4 <50/ml). Mycoplasma, Legionella and

Chlamydia species are uncommon causes. Bacteraemia is com-

moner in HIV-infected patients with bacterial pneumonia, irre-

spective of CD4 count.

The radiographic appearance depends on the underlying

pathogen; both bilateral infiltrates mimicking Pneumocystis

pneumonia and lobar consolidation are seen (Figure 1). Com-

plications include parapneumonic effusion, empyema, intra-

pulmonary cavitation, and abscess formation. There is a high

relapse rate, despite appropriate treatment.

Empirical antibiotics similar to those required in HIV-negative

patients are used for treatment, according to local antibiotic

resistance patterns. Fluoroquinolones should be used with

caution if TB remains within the differential diagnosis.

� 2013 Elsevier Ltd. All rights reserved.

HIV-associated respiratory disease

Infectious disease

C Bacterial

� Acute bronchitis

� Acute and chronic sinusitis

� Bronchiectasis

� Bacterial pneumoniab

C Fungal

� Pneumocystis jirovecii pneumonia (PCP)a

� Cryptococcus neoformans

� Histoplasma capsulatum

C Viral

� Influenza A

C Mycobacterial

� Mycobacterium tuberculosisa

� Atypical mycobacteria

Malignant disease

C Kaposi’s sarcomaa

C Lymphomaa

C Lung cancer

Non-malignant disease

C Fixed obstructive airways disease

C Interstitial lung disease

� Non-specific interstitial pneumonitis

� Lymphoid interstitial pneumonitis

� Sarcoidosis

C Pulmonary arterial hypertension

C Pneumothorax

C Reactions to HIV therapy

� Immune reconstitution inflammatory syndrome

a AIDS-defining illness.b AIDS-defining illness if recurrent episode within 1 year.

Table 1

a

Radiology of bacterial pneumonia in HIV

HIV/AIDS BY SYSTEM

Fungal infections

(a) Chest radiograph showing diffuse, bilateral infiltrates

mimicking Pneumocystis jirovecii pneumonia. The cause was

Streptococcus pneumoniae . (b) Chest radiograph showing lobar

consolidation. The cause was Staphylococcus aureus.

b

Figure 1

Pneumocystis pneumonia: P. jirovecii (previously known as

Pneumocystis carinii) is the cause of Pneumocystis pneumonia

(PCP). In the post-cART era, PCP is seen mainly among those

presenting with a new diagnosis of HIV, and those not receiving

cART and/or prophylaxis due to poor adherence or limited

access to treatment.

The clinical presentation is sub-acutewith several days toweeks

of non-productive cough and progressive exertional dyspnoea,

with or without fever. Chest auscultationmay be normal or reveals

end-inspiratory crackles. Cyanosis may be detected in severe

(hypoxaemic) disease. Themost common chest radiograph finding

is of bilateral perihilar infiltrates (Figure 2).

Atypical findings, such as upper zone infiltrates, hilar/medi-

astinal lymphadenopathy, lobar consolidation, and nodules, are

seen in up to 20%. A normal chest radiograph occurs in 10%,

particularly in those with early presentations, and does not

exclude the diagnosis, but the absence of ground-glass change on

CT makes PCP unlikely.

The gold standard for diagnosis is bronchoalveolar lavage

(BAL) with or without transbronchial biopsy. Sputum induction

MEDICINE 41:8 436

is an alternative. It is not possible to culture the organism, so it

must be seen on microscopy or identified by polymerase chain

reaction analysis. A negative BAL has a high negative predictive

value. Concurrent bacterial pneumonia, TB and Kaposi’s sar-

coma are common.3

Poor prognostic factors identified at presentation, or soon after,

include older age, previous PCP, anaemia, hypoalbuminaemia,

high serum bilirubin or C-reactive protein, hypoxaemia, co-existent

� 2013 Elsevier Ltd. All rights reserved.

Radiology of Pneumocystis pneumonia

Figure 2 (a): Chest radiograph showing diffuse bilateral infiltrates in

Pneumocystis jirovecii pneumonia. (b) Thoracic CT of Pneumocystis jiro-

vecii pneumonia showing bilateral patchy ground-glass infiltrates.

Indications for prophylaxis of Pneumocystispneumonia (PCP) in adult HIV patients

Primary prophylaxis

C CD4 <200/ml

C CD4 <14% total lymphocyte count

C Unexplained fever (>3 weeks’ duration)

C History of oropharyngeal Candida

C History of another AIDS-defining illness (e.g. Kaposi’s sarcoma)

C Consider starting prophylaxis if CD4 count is 200e250/ml but

frequent monitoring is not possible

Secondary prophylaxis

C After an episode of PCP

Table 2

HIV/AIDS BY SYSTEM

pulmonary Kaposi’s sarcoma, and the presence of medical co-

morbidity, such as pregnancy. Subsequent to admission, develop-

ment of pneumothorax, need for admission to the intensive

care unit (ICU), and need for mechanical ventilation are all asso-

ciated with a poor outcome.4 The severity of PCP is clinically

stratified by the degree of hypoxaemia when breathing room

air, into mild (PaO2 >11.0 kPa, SaO2 >96%), moderate (PaO2

8.0e11.0 kPa, SaO2 91e96%) and severe (PaO2<8.0, SaO2<91%).

This grading system is used to guide treatment.

Empirical treatment pending diagnosis is used in those with

typical imaging, CD4 counts less than 200/ml, or clinical stigmata

of immunocompromise (e.g. oral hairy cell leukoplakia, cuta-

neous Kaposi’s sarcoma). High-dose co-trimoxazole (sulphame-

thoxazole 100 mg/kg/day with trimethoprim 20 mg/kg/day, in

two to four divided doses) is the treatment of first choice.5,6 It is

given orally in mild disease or intravenously (IV) in moderate-to-

severe disease, and continued for 21 days. Adverse effects are

MEDICINE 41:8 437

common and include rash, headache, nausea and diarrhoea,

fever, leukopenia and thrombocytopenia, hepatitis, and hyper-

kalaemia. Up to one-third of patients will not complete treatment

due to drug toxicity, and less than 10% will fail treatment

(defined as deterioration after a minimum of 5 days of therapy).

Alternative treatment options for those failing to respond to or

intolerant of co-trimoxazole include clindamycin (450e600 mg

orally or IV 6-hourly) with primaquine (15 mg orally daily), or

dapsone (10 mg orally daily) with trimethoprim (20 mg/kg orally

daily), or atovaquone (750 mg orally 12-hourly) in mild-to-

moderate disease; and clindamycin with primaquine (doses as

above) or pentamidine (4 mg/kg IV daily) in severe disease.

Adjuvant glucocorticoids decrease the risk of respiratory failure

and mortality in severe PCP and should be started within 72

hours, if admission PO2 is 9.3 kPa or lower, or Aea O2 is over 4.7

kPa (breathing room air). Prednisolone 40 mg 12-hourly for

5 days, then 40 mg daily on days 6e10 and 20 mg daily on days

11e21, is the preferred regimen. All patients treated with co-

trimoxazole, dapsone, and primaquine should be screened for

glucose-6-phosphate dehydrogenase deficiency.

It is recommended that patients begin cART before completing

treatment for the episode of PCP. There is limited evidence for

starting cART among HIV patients with opportunistic infections

who are critically unwell and admitted to the ICU. In this context,

some clinicians advocate delaying treatment until the patient has

left the ICU, and is showing signs of recovery.

Indications for prophylaxis of PCP are listed in Table 2. Co-

trimoxazole is the treatment of first choice, and also protects

against several bacterial infections and toxoplasmosis. Alterna-

tive prophylaxis regimens include nebulized pentamidine, once

per month via a jet nebulizer (once per fortnight if CD4 <50/ml),

dapsone with pyrimethamine, and atovaquone.7

Prophylaxis can be discontinued if the CD4 count rises to above

200/ml with an undetectable plasma HIV-RNA for more than

3 months on cART, although there is some evidence that dis-

continuing at a CD4 count of over 100/ml is safe if viraemia is fully

suppressed. If the CD4 count falls later, recommencement of pro-

phylaxis should be considered.7

Other fungal infections: Cryptococcus neoformans causes pul-

monary infection when the CD4 count is below 200/ml. This can

� 2013 Elsevier Ltd. All rights reserved.

HIV/AIDS BY SYSTEM

be isolated, or occur as part of disseminated disease with men-

ingitis, with or without cryptococcaemia. Chest radiographic

changes include diffuse bilateral infiltrates mimicking PCP, focal

infiltrates, nodules, mass lesions, cavities, pleural effusions, and

lymphadenopathy. Diagnosis is made by identifying of C. neo-

formans in sputum or BAL. Treatment for disseminated disease is

with amphotericin/flucytosine followed by fluconazole, or with

fluconazole alone in isolated pneumonia.

Histoplasma capsulatum and Coccidioides immitis are

endemic in parts of Africa and The Americas. Both present with

disseminated disease in persons with CD4 counts below 200/ml,

but can cause focal pneumonia in those with CD4 counts greater

than 200/ml. Presentation is often non-specific with fever and

weight loss. Diagnosis requires culture of sputum, BAL fluid, or

transbronchial biopsy for both organisms. Serum (1e3)-b-D-

glucan may be elevated in histoplasmosis, but is non-specific.

Treatment requires a prolonged course of antifungal medication

until a sustained improvement in CD4 count and HIV-RNA level

has been achieved.8

Viral infections

Influenza A: there is no evidence that influenza A is more

common in HIV-infected persons, but those with lower CD4

counts may experience more severe disease and infection may be

complicated by secondary bacterial pneumonia. Patients with

both seasonal and H1N1 influenza present with coryzal symp-

toms, myalgia, fever and headache. As for the general popula-

tion, treatment with neuraminidase inhibitors should be given

if influenza A is suspected or confirmed, and is most effective

if started within 48 hours of symptom onset. Diagnosis is

confirmed when viral antigen or RNA is detected in a nasopha-

ryngeal aspirate or nasal swab. HIV-infected patients may

continue to excrete influenza A in respiratory secretions for

prolonged periods, despite clinical recovery.

Mycobacterial infections

Mycobacterium tuberculosis: TB occurs between 20 and 40 times

more frequently in HIV-infected persons, can occur at any stage

of HIV, is an AIDS-defining illness regardless of CD4 count, and is

a notifiable disease in the USA, the UK and most European

countries. Worldwide about 15% of new TB cases occur in HIV-

infected persons, and TB is the cause of about 25% of all adult

HIV-related deaths.

Latent TB infection (LTBI): the annual risk of progression from

latent to active disease is high in HIV-positive individuals,

estimated at 10% per annum, and is greater with lower CD4

counts. Long-term treatment with cART significantly decreases

this risk, but does not restore it to that of an HIV-negative

person. Acutely, cART may increase the risk of TB, so-called

unmasking disease. HIV-positive individuals who have a high

risk of latent TB due to their country of origin, and a high risk

of reactivation of disease due to a low CD4 count or limited

time on cART, should therefore be screened and treated for

LTBI. Interferon-g release assays (IGRA) are more specific than

the tuberculin skin test for screening for LTBI, and retain

sensitivity at low CD4 counts. Chemoprophylaxis regimens

include isoniazid for 6 months, and rifampicin with isoniazid

for 3 months.

MEDICINE 41:8 438

Active TB: more than two-thirds of cases of active TB in HIV-

infected patients present with pulmonary disease. Extra-

pulmonary disease is common in patients with CD4 counts

below 150/ml and may involve lymph nodes, bone marrow, liver

and pericardium.

In patients with early HIV disease and maintained CD4

counts, the clinical picture of pulmonary TB is similar to adult

post-primary disease. Symptoms include chronic cough, dysp-

noea, haemoptysis, chest pain, fever, sweats, and weight loss.

Chest radiographs may show apical change and cavitation.

Sputum and BAL are often smear and culture positive. In more

advanced disease with low CD4 counts, the presentation is often

atypical and symptoms less specific. Chest radiographs may be

normal but tend to represent primary disease with mediastinal

and hilar lymphadenopathy, miliary patterns, and pleural effu-

sions. Cavitation is less likely, due to a lower grade immune

response to the organism, and sputum and BAL are often smear

negative but culture positive.

As in HIV-negative groups, culture remains the gold standard

for diagnosing active disease. Molecular diagnostic tests can be

used on respiratory samples and provide results within hours.

Although increasingly sensitive, they cannot be used to exclude

the diagnosis if negative. They not only enable rapid identification

of M. tuberculosis versus atypical mycobacteria, but also identify

mutations in the rpoB, inhA and katG genes associated with drug

resistance. The role of IGRA in the diagnosis of active tuberculosis

in HIV-infected persons remains uncertain.

While awaiting species identification, all acid- and alcohol-fast

bacilli, regardless of CD4 count, should be treated empirically as

M. tuberculosis, with standard TB treatment (2 months of rifam-

picin, isoniazid, ethambutol and pyrazinamide, followed by a

further 4 months of isoniazid and rifampicin). Daily treatment is

preferred over intermittent treatment because of concerns about

development of drug resistance patients with a highmycobacterial

burden. Some authorities advocate extending the continuation

phase to seven months in patients with cavitating pulmonary

disease and where sputum remains smear positive at 2 months. In

central nervous system disease, treatment is for 12 months.

Adverse events, drug reactions and mortality are more frequent

compared with non-HIV-infected individuals. Following treat-

ment, secondary prophylaxis of TB is not given in UK; its role in

areas with high rates of re-infection remains unclear.

Multidrug-resistant and extensively drug-resistant tubercu-

losis have been epidemiologically associated with HIV infection.

This is probably due to rapid development of active tuberculosis

in HIV co-infected persons exposed to drug-resistant cases, rather

than any predilection to infection with drug-resistant strains.

Timing of cART in patients being treated for TB: cART should be

started in all HIV-infected patients treated for active TB. cART

reduces short- and long-termmortality in co-infected persons.9 TB

treatment should be initiated first, with cART shortly after e the

interval allowed between introduction of these regimens varies,

and is determined largely by the patient’s immune status (i.e. the

lower the CD4 count the sooner cART is started). Problems

encountered when treating TB and starting cART include high pill

burden, and hence poor adherence, overlapping toxicities (e.g.

peripheral neuropathy), drugedrug interactions (e.g. rifampicin

and protease inhibitors) and immune reconstitution inflammatory

� 2013 Elsevier Ltd. All rights reserved.

HIV/AIDS BY SYSTEM

syndrome (IRIS). Early initiation of cART has been shown to have

a survival benefit for patients with low CD4 counts, whereas in

thosewith higher CD4 counts the risk of HIV disease progression is

lower and the survival benefit of early cART less certain, such that

HIV treatment can be delayed.10e12 Current UK guidelines are

listed in Table 3. The timing of cART in TB meningitis remains

controversial.13

Atypical mycobacteria: non-tuberculous mycobacterial infection

is rare among HIV-infected patients.M. avium complex (M. avium

or Mycobacterium intracellulare) is the most common form and

causes disseminated disease or localized lymphadenitis, particu-

larly among those with CD4 counts below 50/ml. It is diagnosed by

blood or tissue culture. Mycobacterium kansasii presents with

disseminated or pulmonary disease. The latter may be indistin-

guishable from M. tuberculosis on imaging, thus diagnosis relies

on culture and speciation.

Immune reconstitution inflammatory syndrome (IRIS): when

cART is introduced after treatment for an opportunistic infection

is started, a paradoxical deterioration of symptoms known as IRIS

(see Immune response to HIV and vaccination on pages 425e429

of this issue) may be seen, often after initial improvement.14

IRIS may present as a respiratory syndrome with new or wors-

ening lymphadenopathy, pleural/pericardial effusions, or wors-

ening clinical or radiographic, features of the underlying

opportunistic infection. In the context of TB, two patterns of IRIS

are encountered. First, a paradoxical type, similar to paradoxical

reactions seen in the non-HIV-infected population, but often more

pronounced; in this form of IRIS, patients develop new clinical

manifestations (e.g. new lymphadenopathy) a median of 2e3

weeks after starting cART. Second, patients with latent asymp-

tomatic TB infection may experience ‘unmasking’ IRIS, with

development of highly inflammatory active TB a median of 3e6

weeks after commencing cART.

Should IRIS develop, the aim should be to continue both

treatment of the initial infection, and cART, unless IRIS is severe

or life-threatening (e.g mediastinal or intracerebral disease

causing mass-effect). Treatment of IRIS is often symptomatic, but

in patients with worsening intracerebral or mediastinal disease

systemic corticosteroids should be used.15

Preventing respiratory infections

Bacteria: immunization with pneumococcal vaccine is recom-

mended at diagnosis of HIV (irrespective of CD4 count) and

5-yearly thereafter. Conjugate vaccines may offer better

Timing of cART in TB/HIV co-infection20

CD4 count (cells/ml) Initiation of cART

<100 As soon as practicable

100e350 As soon as practicable

Can wait until 8/52, especially

if difficulties with drug interactions,

drug adherence, and drug toxicities

>350 At physician’s discretion

Table 3

MEDICINE 41:8 439

protection than polysaccharide. Clinical efficacy and humoral

responses are likely to be impaired in those with CD4 counts

below 200/ml. Haemophilus influenzae b vaccine is not indicated.

Tuberculosis: BCG is a live vaccine, and its efficacy in HIV-

infected patients is unknown. Given the risk of disseminated

disease it is not recommended in HIV-infected persons.

Influenza: all HIV-infected patients should be given the annual

intramuscular influenza vaccination. The live attenuated intra-

nasal vaccine should be avoided.

Malignant disease

Pulmonary Kaposi’s sarcoma

Kaposi’s sarcoma (KS) is the most common HIV-associated

malignancy. General aspects are discussed elsewhere (see AIDS-

related malignant disease on pages 430e434 of this issue). Pul-

monary involvement with KS is almost always accompanied by

cutaneous or lymphadenopathic KS, and palatal disease strongly

predicts the presence of pulmonary disease. Presentation is with

progressive dyspnoea and non-specific cough; haemoptysis is

uncommon. Pulmonary KS may affect the airways, parenchyma,

pleura, or intra-thoracic lymph nodes. Radiological abnormalities

include nodular or interstitial infiltrates, pleural effusion (up to

40%), and mediastinal/hilar lymphadenopathy (w25%). Diag-

nosis is confirmed on bronchoscopywheremultiple, red or purple,

flat or raised endotracheal or endobronchial lesionsmay be seen in

up to 50% (Figure 3). Biopsy has a low yield and is rarely per-

formed. Pleural biopsy or cytology is rarely diagnostic. cART may

induce remission of lesions. Chemotherapy is given for symp-

tomatic or extensive parenchymal disease at presentation, or dis-

ease that progresses despite cART. Kaposi’s sarcoma-associated

pleural effusions are difficult to treat, medical pleurodesis is

seldom successful, and repeat thoracocentesis is often required.

Lymphoma

High-grade non-Hodgkin’s B cell lymphoma is the most common

intra-thoracic lymphoma. Hodgkin’s lymphoma also occurs with

increased frequency among HIV-infected individuals. Lung pa-

renchyma, pleura (effusion or mass), and mediastinal/hilar

lymph nodes may be involved. Extra-thoracic disease is usually

evident at diagnosis. Outcome from chemotherapy is better if

cART is also given.

Lung cancer

Lung cancer is the most common non-AIDS-defining cancer

among HIV-infected persons in the developed world.16 The

incidence is higher among the HIV-infected than the general

population, an effect only partially explained by tobacco smok-

ing. In the cART era the incidence appears to be increasing.17

Clinical presentation is often with extensive local or metastatic

disease with a poor prognosis, which is not improved by starting

cART.

Non-malignant disease

Airways disease

The prevalence of fixed airway obstruction and diffusion impair-

ment is higher in the HIV-infected population.18 HIV-infected

� 2013 Elsevier Ltd. All rights reserved.

(a) Chest radiograph showing multiple, nodular infiltrates in a

patient with pulmonary Kaposi’s sarcoma. (b) Endobronchial

lesions of pulmonary Kaposi’s sarcoma.

b

a

Pulmonary Kaposi's sarcoma

Figure 3

HIV/AIDS BY SYSTEM

cigarette smokers are twice as likely as smokers without HIV

infection to have chronic obstructive pulmonary disease (COPD).

Additional factors including substance misuse, recurrent oppor-

tunistic and bacterial infections and direct inflammatory effects of

HIV and cARTmay also contribute.19 Smoking cessation should be

encouraged.

Interstitial lung disease

Non-specific interstitial pneumonitis: non-specific interstitial

pneumonitis presents with symptoms and chest radiographic ab-

normalities that mimic PCP, but it often occurs at higher CD4

counts. Diagnosis requires transbronchial or video-assisted thor-

acoscopic surgery (VATS) lung biopsy. Episodes are usually self-

limiting but prednisolone may be beneficial.

MEDICINE 41:8 440

Lymphocytic interstitial pneumonitis: lymphocytic interstitial

pneumonitis is more common in HIV-infected children, particu-

larly those with perinatal infection, than in adults. Patients pre-

sent with cough and dyspnoea. Chest examination is often

normal. Imaging shows diffuse reticulo-nodular infiltrates, or

may mimic PCP. Diagnosis is made by biopsy. Treatment with

cART is often effective.

Sarcoidosis: before the era of cART, sarcoidosis was rarely

described. In the era of cART it is increasingly recognized and is

thought to represent an immune reconstitution phenomenon.

Presentation is with cough and dyspnoea; the CD4 count is

usually greater than 200/ml. Imaging shows bilateral hilar

lymphadenopathy, with or without reticulo-nodular shadowing.

Symptoms may be self-limiting, but prednisolone may be

required.

Pulmonary arterial hypertension

Pulmonary arterial hypertension occurs more commonly among

HIV-infected patients than in the general population (estimated

prevalence 0.5%). Presentation, imaging, ECG, and echocardio-

graphic findings are similar to those seen in the general popu-

lation. Secondary causes of pulmonary arterial hypertension, for

example chronic thromboembolic disease, should be excluded.

Treatment is as for the general population; additionally, cART is

associated with improved haemodynamics and survival.

Pneumothorax

Pneumothorax occurs more commonly in HIV-infected persons

than in the general population. Risk factors include cigarette

smoking and nebulised pentamidine. PCP should be excluded in

any patient presenting with a pneumothorax.

Conclusions

Among HIV-infected populations with access to cART, the spec-

trum of HIV-associated lung disease has changed, such that PCP is

less commonly seen, but patients with undiagnosed/declared HIV

infection continue to present with respiratory symptoms, to both

primary care and to emergency departments. Among this popula-

tion a wide differential diagnosis exists. Any adult presenting with

severe or atypical respiratory disease should be offered anHIV test,

irrespective of the presence/absence of stigmata of immune sup-

pression, in keeping with UK British Association for Sexual Health

and HIV (BASHH)/British HIV Association (BHIVA) national

guidelines. A

REFERENCES

1 Morris A, Crothers K, Beck JM, Huang L, American Thoracic Committee

on HIV Pulmonary Disease. An official ATS workshop report:

emerging issues and current controversies in HIV-associated pulmo-

nary diseases. Roc Am Thorac Soc 2011; 8: 17e26.

2 Crothers K, Thompson BW, Burkhardt K, et al. International HIV

associated opportunistic pneumonias (IHOP) study; lung HIV study.

HIV-associated lung infections and complications in the era of com-

bined antiretroviral therapy. Proc Am Thorac Soc 2011; 8: 275e81.

3 Huang L, Cattamanchi A, Davis JL, et al. International HIV associated

opportunistic pneumonias (IHOP) study; lung HIV study.

� 2013 Elsevier Ltd. All rights reserved.

Practice points

C Although the use of cART has decreased the rate of pulmonary

infection, it exceeds that of the general population. A high

index of suspicion must be maintained and investigations

including CT imaging and bronchoscopy with bronchoalveolar

lavage may be required

C Concurrent use of cART is advised when treating opportunistic

respiratory infections

C Patients should be monitored for the development of immune

reconstitution inflammatory syndrome, particularly if starting

CD4 count is low, the burden of initial infection is high, and the

CD4 count rapidly recovers

C TB-HIV co-infection should be managed in a specialist centre e

concurrent use of cARTand anti-tuberculosis medications can be

challenging

C More attention must be paid to aspects of general lung health

such as smoking cessation in HIV-infected populations, as life

expectancies increase and chronic non-infectious conditions

such as chronic obstructive pulmonary disease (COPD) and

primary lung cancer become more common

HIV/AIDS BY SYSTEM

HIV-associated pneumocystis pneumonia. Proc Am Thorac Soc 2011;

8: 294e300.

4 Armstrong-James D, Copas AJ, Walzer PD, et al. A prognostic scoring

tool for identification of patients and high and low risk of death from

HIV-associated Pneumocystis jirovecii pneumonia. Int J STD AIDS

2011; 22: 628e34.

5 British HIV Association and British Infection. Association guidelines

for the treatment of opportunistic infection in HIV-seropositive in-

dividuals 2011.

6 Morbidity and Mortality Weekly Report. Guidelines for prevention and

treatment of opportunistic infections in HIV-infected adults and ad-

olescents recommendations from CDC, the National Institutes of

Health, and the HIV Medicine Association of the infectious diseases

Society of America, www.cdc.gov/mmwr; 2009.

7 Kaplan JE, Benson C, Holmes KH, et al. Centres for Disease Control

and Prevention (CDC); National Institutes of Health. HIV Medicine

Association of the Infectious Diseases Society of America. Guidelines

for prevention and treatment of opportunistic infections in HIB-

infected adults and adolescents: recommendations from CDC, the

National Institutes of Health, and the HIV Medicine Association of the

Infectious Diseases Society of America. MMWR Recomm Rep 2009;

58(RR-4): 1e207.

8 Huang L, Crothers K. HIV-associated opportunistic pneumonias.

Respirol 2009; 14: 474e85.

9 Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of

antiretroviral drugs during tuberculosis therapy. New Engl J Med

2010; 362: 697e706.

10 Abdool Karim SS, Naidoo K, Grobler A, et al. Integration of an-

tiretroviral therapy with tuberculosis treatment. New Engl J Med

2011; 365: 1492e501.

11 Havlir DV, Kendall MA, Ive P, et al. Timing of antiretroviral therapy

for HIV-1 infection and tuberculosis. New Engl J Med 2011; 365:

1482e91.

12 Xavier Blanc F, Sok T, Laureillard D, et al. Earlier versus later start of

antiretroviral therapy in HIV-infected adults with tuberculosis. New

Engl J Med 2011; 365: 1471e81.

13 Lawn SD, Torok ME, Wood R. Optimum time to start antiretroviral

therapy during HIV-associated opportunistic infections. Curr Opin

Infect Dis 2011; 24: 34e42.

14 Lipman M, Breen R. Immune reconstitution inflammatory syndrome in

HIV. Curr Opin Infect Dis 2006; 19: 20e2514.

15 Meintjes G, Wilkinson RJ, Morroni C, et al. Randomized placebo-

controlled trial of prednisone for paradoxical tuberculosis-

MEDICINE 41:8 441

associated immune reconstitution inflammatory syndrome. AIDS

2010; 24: 2381e90.

16 Engels EA. Non aids-defining malignancies in HIV-infected persons:

etiological puzzles, epidemiological perils, prevention opportunities.

AIDS 2009; 23: 875e85.

17 Kirk GD, Merlo CA. International HIV associated opportunistic pneu-

monias (IHOP) study; lung HIV study. HIV infection in the etiology of

lung cancer: confounding, causality, and consequences. Proc Am

Thorac Soc 2011; 8: 326e32.

18 Gingo MR, George MP, Kessinger CJ, et al. Pulmonary function ab-

normalities in HIV-infected patients during the current antiretroviral

therapy era. Am J Respir Crit Care Med 2010; 182: 790e6.

19 Morris A, George MP, Crothers K, et al. International HIV associated

opportunistic pneumonias (IHOP) study; lung HIV study. HIV and

chronic obstructive pulmonary disease e is it worse and why? Proc

Am Thorac Soc 2011; 8: 320e5.

20 Pozniak AL, Coyne KM, Miller RF, et al. BHIVA treatment guidelines for

TB/HIV infection 2011. HIV Med 2011; 12: 517e24.

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