Even with advances in antiretroviral therapy, pulmonary complications of AIDS remain an important cause of morbidity and mortality among HIV-infected individuals. Interpretation of imaging studies should integrate demographic, clinical, and laboratory information with radiographic pattern recognition. The authors present the various pulmonary complications of AIDS, with a particular emphasis upon recent trends in imaging features of pulmonary disorders, as shown on chest radiography and computed tomographic examinations.
is a Specialist in Radiology Chest and Cardiovascular Imaging in
the Department of Radiology, Tel Aviv Sourasky Medical Center,
Tel Aviv University, Tel Aviv, Israel;
is an Assistant Professor of Radiology in the Department of
Radiology, Jackson Memorial Hospital, University of Miami, Miami,
he Director of Thoracic Imaging and Co-Director of the Residency
Program in the Department of Radiology, Beth Israel Deaconess
Medical Center, and Assistant Professor of Radiology at Harvard
Medical School, Boston, MA.
During the two decades since the emergence of the acquired
immune deficiency syndrome (AIDS), many changes have been noted in
the demographics, complications, and treatment of this epidemic.
It is important to be aware that AIDS is no longer a disease
confined to the homosexual male population. Indeed, in the past
decade, there has been an increasing prevalence of AIDS among
intravenous drug abusers and women.
The introduction of highly active antiretroviral therapy (HAART)
has been associated with a dramatic reduction in human
immunodeficiency virus (HIV)-associated morbidity and mortality.
By effectively suppressing viral replication, HAART results in a
decrease in viral load and a rise in the CD4 lymphocyte count, with
an associated reduced prevalence of various opportunistic
infections and certain neoplasms. Following dramatic reductions in
the number of new AIDS cases and deaths in the United States in the
mid-1990s, a plateau in morbidity and mortality was observed at the
end of the last decade.
Importantly, the battle against AIDS looms largely on a global
basis, with continued explosive growth of the epidemic in the
setting of significant barriers to antiretroviral therapy.
Pulmonary disorders, particularly respiratory infections, remain
an important cause of morbidity and mortality among HIV-infected
individuals, even in the current era of potent antiretroviral
therapy. Interestingly, demographic and therapy changes of HIV
infection have been accompanied by changes in the frequency and
nature of the pulmonary complications of AIDS and their imaging
In this article, we review the various pulmonary complications of
AIDS, with a particular emphasis upon recent trends in imaging
features of pulmonary disorders as shown on chest radiography and
computed tomography (CT) examinations.
Approach to imaging diagnosis
Because the various pulmonary complications of HIV occur with
different frequencies among patients with specific risk factors,
different levels of immune compromise, and various prophylactic
therapies, one should combine all these factors along with the
clinical presentation and the recognized radiographic pattern in
order to reach the most likely correct diagnosis.
Of these parameters, the patient's immune status, as reflected by
the serum CD4 lymphocyte count, is considered the most important
determinant for assessing the relative likelihood of various
pulmonary complications (Table).
Chest radiography is usually the first imaging test obtained for
the assessment of an HIV-infected individual with respiratory
symptoms. Despite atypical manifestations and overlapping features
among several entities, the chest radiograph is fairly accurate for
diagnosing common complications.
Even in asymptomatic HIV patients, an abnormal chest radiograph
usually signifies an active process.
CT is considered as a second-line study for problems unresolved by
chest radiography. CT, particularly using high resolution (HRCT),
is more sensitive in detecting various opportunistic infections
when the chest radiograph is normal.
CT is also very useful in assessing patients for complications of
pneumonia, such as abscess and empyema; in detecting and
characterizing enlarged intrathoracic lymph nodes; and in staging
Infectious lung diseases in AIDS
Although mainly cell-mediated immunity is impaired in HIV
infection, humoral immunity is also altered.
In particular, B-cell dysfunction is associated with high risk for
frequent infections with encapsulated bacteria, such as
In recent years, bacterial infections, including infectious airways
disease and pneumonia, have surpassed
pneumonia (PCP) as the most common cause of pulmonary infection in
Although bacterial pneumonia often occurs early in the course of
HIV, the risk for this infection progressively increases with
decreasing CD4 counts.
Most episodes of pneumonia occur secondary to
, the same organisms that cause most community-acquired pneumonia
in the general population.
has also recently been recognized as a cause of pulmonary infection
in AIDS, especially among patients with a recent history of
hospitalization, antibiotic use, or steroid therapy.
AIDS patients are also at risk for infection with unusual zoonoses
an organism that is more commonly encountered in horses, cattle,
and swine, and
, the causative agents of bacillary angiomatosis.
Patients with bacterial pneumonia typically present with an
acute onset of fever and productive cough.
In most cases, bacterial pneumonia presents radiographically as
single or multiple sites of focal consolidation, in either a
segmental or lobar distribution
(Figure 1). Atypical patterns, including bilateral diffuse
opacities, are not uncommon.
Importantly, complications, such as bacteremia and abscess, develop
more often in HIV-infected individuals with bacterial pneumonia
than in non-HIV patients.
Pyogenic infectious airways diseases, including infectious
bronchitis, bronchiolitis, and bronchiectasis, have been
increasingly recognized in HIV-positive patients in recent years.
Chest radiographs of patients with acute bacterial bronchitis are
usually normal, but may show bronchial wall thickening.
In contrast, the high-resolution CT features of infectious
bronchiolitis are characteristic and include small nodular and
branching, Y- and V-shaped centrilobular opacities, which represent
bronchioles that are impacted with inflammatory secretions. This
pattern has been coined the tree-in-bud appearance.
Although pyogenic infections are the most common cause of
proliferative small airways disease in AIDS patients, viral and
mycobacterial infections may produce similar imaging findings.
pneumonia remains the most common serious AIDS-related
opportunistic infection, despite a declining incidence secondary to
HAART and prophylactic use of trimethoprim-sulfamethoxazole
pneumonia usually occurs in persons not receiving medical care,
and whose CD4 counts are <200 cells/mm
Affected patients generally present with a hi tory of approximately
1 month of fever, dry cough, and dyspnea.
The classic chest radiographic presentation of PCP is a
bilateral perihilar or diffuse symmetric interstitial pattern,
which may be finely granular, reticular, or ground-glass in
(Figure 2A). Importantly, the chest radiograph may be normal in
approximately one-third of cases at the time of presentation.
CT, particularly HRCT, is very helpful in detecting PCP in
symptomatic patients with normal or equivocal radiographic
The classic HRCT finding in PCP is extensive ground-glass
attenuation (Figure 2B). It is often distributed in a patchy or
geographic fashion, with a predilection for the central, perihilar
regions of the lungs.
Cystic lung disease is observed in up to one-third of cases (Figure
3), and may be complicated by pneumothorax.
As tuberculosis (TB) is both highly curable and contagious,
prompt diagnosis and treatment are essential.
The HIV-infected individuals at particularly high risk for TB
include intravenous drug abusers and patients from areas where TB
Tuberculosis can occur at any stage of HIV infection.
In fact, reactivation (postprimary) TB is often one of the initial
manifestations of HIV infection. Presenting symptoms may include
more than a week of cough, night sweats, and weight loss.
Typical imaging features include parenchymal opacities with
associated cavitation, often located within the apical, posterior,
and superior segments of the lungs.
In patients with decreased CD4 counts (<200 cells/mm
), one will observe findings typically associated with primary TB
(regardless of the actual mechanism of infection), including
consolidation and lymph-node enlargement.
At advanced levels of immune suppression, a minority of patients
may have normal chest radiographs, though CT will often show
abnormalities such as small nodules and lymph node enlargement.
The immune reconstitution syndrome (also known as reversal
syndrome) refers to a newly described phenomenon that may be
observed in AIDS patients who are being treated for tuberculosis
infection and are also receiving antiretroviral therapy.
In the setting of immune restoration, such patients may exhibit new
or worsening lymph node enlargement, lung paren-chymal disease,
and/or pleural effusions, accompanied by onset of fever (Figure 4).
Such paradoxical reactions are thought to be immunologically
mediated by a heightened immune response.
The diagnosis requires exclusion of other important causes,
including noncompliance with therapy, drug resistance, other
superimposed disease process, and drug reaction.
Atypical mycobacterial infections
Atypical mycobacterial infections in AIDS patients are usually
(MAI) and, less commonly, due to
Because MAI is a less virulent organism than
, it is usually encountered in the setting of more advanced
immunosuppression (CD4 <50/mm
Thoracic MAI involvement usually occurs in the setting of
disseminated disease, with the gastrointestinal tract serving as
the main entry site in most cases. Imaging findings in the lungs
are variable and include multifocal patchy consolidation,
ill-defined nodules, and cavities.
Lymphadenopathy is frequently present, but is observed less
frequently than it is in patients with TB.
Fungal infections are a relatively uncommon cause of pulmonary
infection in AIDS patients but are more prevalent in endemic areas.
The most common fungal pathogen to involve the lungs in AIDS
Less common fungal infections include aspergillosis,
histoplasmosis, blastomycosis, and coccidiomycosis. Fungal
pulmonary infection usually occurs in the setting of advanced
immunosuppression (CD4 <100/mm
). Imaging findings include nodules, reticular or reticulonodular
opacities, and foci of consolidation (Figure 5).
Parenchymal abnormalities may be accompanied by lymph node
enlargement and pleural effusion.
Although infection with
is uncommonly encountered in AIDS, its incidence is increasing.
This infection occurs almost exclusively in HIV-positive
individuals with CD4 counts <50 cells/mm
The most common imaging presentation is cavitary disease with an
upper lobe predominance.
Cytomegalovirus (CMV) is the most common viral agent identified
in the lungs of AIDS patients.
However, it is much more frequently a colonizer than an actual
cause of pneumonia. Cytomegalovirus pneumonitis occurs in patients
with advanced levels of immunosuppression (CD4 <100/mm
) who almost always have documented extrathoracic CMV infection.
The most common imaging features of CMV pneumonitis are
ground-glass opacities and alveolar consolidation, which may mimic
Other imaging findings include nodules, masses, and small airways
Noninfectious lung diseases in AIDS
Early in the AIDS era, up to 40% of homosexual men presented at
the time of their initial AIDS diagnosis with Kaposi's sarcoma
Subsequently, there has been a continuous decrease in the incidence
of KS among HIV-infected people, from approximately 10% to 20% in
the early 1990s to even lower levels at present.
Kaposi's sarcoma is a multicentric disease that frequently involves
the skin, lymph nodes, gastrointestinal tract, and lungs. Pulmonary
KS in the absence of mucocutaneous involvement is uncommon.
The CD4 cell count in patients with pulmonary KS is usually <100
The most common presenting symptoms of pulmonary KS are dyspnea
and cough; hemoptysis is less common.
Characteristic findings on chest radiography include thickening
along the peribronchovascular bundles, often in the perihilar
regions. As the tumor grows, reticulonodular opacities may appear,
mainly in the lower lobes. The interstitial and ill-defined nodular
opacities may coalesce to form dense areas of alveolar
consolidation. Thickened interlobular septae are commonly observed.
Pleural effusions are also common; they may be unilateral or
bilateral and may vary considerably in size.
CT of the chest offers additional benefits over conventional chest
radiography by revealing mediastinal lymphadenopathy, which is
present in 50% of cases, and improved characterization of the
bronchovascular pattern of lung parenchymal opacities.
Non-Hodgkin's lymphoma (NHL) is the second most common
malignancy in AIDS, occurring in 2% to 10% of HIV-infected
The incidence of lymphomas in AIDS patients may be on the rise due
to longer life expectancies in AIDS.
However, there is conflicting data regarding the relative incidence
of NHL in the HAART era as compared with previously.
The disease is twice as common in whites and males than in African
Americans and women, respectively.
AIDS-related NHL usually affects patients with CD4+ levels <100
At presentation, 75% of the patients are at advanced stage (stage 3
or 4), and constitutional B-cell symptoms are commonly reported.
Extranodal involvement of the central nervous system,
gastrointestinal tract, and bone marrow are frequently observed.
Pulmonary involvement is clinically diagnosed in only 6% to 10%
of AIDS patients with NHL.
The most common symptoms are cough, dyspnea, and pleuritic chest
Intrathoracic NHL in AIDS is most often extranodal.
The most common radiologic findings consist of multiple pulmonary
nodules, areas of consolidation, and pleural effusions.
Reticular opacities and masses are also observed relatively
With regard to lung nodules, they are usually well circumscribed
and range in size from 0.5 to 5 cm in diameter; air bronchograms
are frequently present, and a halo of ground-glass attenuation may
be observed around the nodules on thin-slice CT.
One distinctive form is primary pulmonary AIDS-related lymphoma,
which is defined by exclusive lymphomatous parenchymal involvement
with no other sites of involvement identified up to 3 months
(Figure 6). CT shows mediastinal and hilar lymph-adenopathy in
approximately half of patients imaged.
AIDS-related NHL may occasionally present as a mediastinal mass in
the absence of pulmonary parenchymal disease (Figure 7).
Epidemiological surveys continue to debate a possible link
between HIV infection and an increased risk for the development of
It is generally accepted that patients with lung cancer and HIV
infection are often younger, present at a more advanced stage, and
have a more fulminant course of disease than the general population
with lung cancer.
Similar to the general population, lung cancer occurs in HIV in
association with cigarette smoking, and adenocarcinoma is the most
common cell type.
Prognosis has historically been considered dismal, but a recent
report suggests that the disease may be treatable in the short- or
The most frequent radiographic presentation, similar to
HIV-negative individuals, is a central or peripheral mass (Figure
Ipsilateral hilar and variable mediastinal lymphadenopathy,
postobstructive consolidation or atelectasis, and pleural effusion
or pleural mass are also common.
Lymphocytic interstitial pneumonia
Lymphocytic interstitial pneumonia (LIP) is characterized by
interstitial lung infiltration by mature lymphocytes and plasma
cells creating peribronchovascular nodules without airspace
Lymphocytic interstitial pneumonia is seen in 30% to 40% of
pediatric HIV-infected patients with pulmonary disease but less
frequently in adults with AIDS.
Patients may be asymptomatic or show an insidious onset of
respiratory distress with cough and mild hypoxemia.
Characteristic findings on chest radiography consist of fine or
coarse reticular and nodular opacities (Figure 9) with an
occasional alveolar component.
CT reveals ill-defined 2- to4-mm nodules, often in
peribronchovascular distribution and bilateral areas of
On thin-section CT, poorly defined centrilobular nodules involving
all lung zones can be identified.
Thickening of bronchovascular bundles, thickened septal lines,
small subpleural nodules, and cystic air spaces are also observed
in a majority of patients. Mediastinal or hilar lymphadenopathy is
Recently published reports suggest that there may be an
increased susceptibility to pulmonary emphysema among HIV-positive
smokers (Figure 10).
A comparison between a cohort of HIV-positive patients without
history of pulmonary complications and HIV-negative controls
revealed an incidence of emphysema of 15% among the HIV patients
and only 2% among the control subjects.
It is possible that the pathogenesis of emphysema is accelerated by
the attendant pulmonary infections.
As survivial of HIV patients increases due to HAART,
cardiovascular complications are becoming more manifest in these
patients. Some of these many entities include cardio-myopathy,
pulmonary artery hypertension, and atherosclerosis, the latter
possibly related to protease inhibitor therapies.
It has also been suggested that venous thromboembolic disease (deep
venous thrombosis and pulmonary embolism) is of increased incidence
in HIV-positive patients (Figure 11).
Possible links between cardiovascular diseases and HIV are the
subject of ongoing investigation.
Even in the current era of potent antiretroviral therapy,
pulmonary complications of AIDS remain an important cause of
morbidity and mortality among HIV-infected individuals.
Interpretation of imaging studies should integrate demographic,
clinical, and laboratory information with radiographic pattern
recognition. Although chest radiography remains the mainstay of
thoracic imaging in HIV-infected patients, CT plays an
in-creasingly important complementary role in establishing an
accurate diagnosis when chest radiographic findings are equivocal