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Chest Imaging Findings for Evaluation HIV-related
Pulmonary Diseases Comparing between Patients
Receiving and Non-Receiving Antiretroviral Therapy
Yutthaphan Wannasopha MD a, *, Natthaphong Nimitrungtavee MD a, Juntima Euathrongchit
MD a, Apichat Tantraworasin MD b
a Department of Radiology, Faculty of Medicine, Chiang Mai University, Thailand
b General Thoracic Unit , Department of Surgery, Faculty of Medicine, Chiang Mai
University, Thailand
Abstract
Objective: To compare chest imaging findings in HIV-related pulmonary diseases presenting
with chest symptoms between patients receiving and non-receiving anti-retroviral therapy
(ART).
Materials and methods: From August 2010 to August 2015, the chest radiographs or chest
computed tomography (CT) of 174 HIV infected patients who had chest symptoms (cough,
dyspnea and hemoptysis) in Maharaj Nakorn Chiangmai hospital were retrospectively
reviewed by three blinded reviewers with consensus. Presence and character of opacities,
nodules, cavities, pleural effusion, pneumothorax and adenopathy were documented in each
patient. All of the patients have been diagnosed of HIV-related pulmonary diseases which
confirmed by laboratory investigations, cytology, pathology or improvement of clinical or
imaging after treatment.
Results: Of the 174 HIV-infected patients, 59 (33.9%) had been received ART with good
compliance and 115 (66.1%) were non-receiving ART patients. The median CD4 lymphocyte
count was statistically significant higher in patients receiving ART. The most common HIVrelated pulmonary disease was Pneumocystis jiroveci pneumonia (PCP) in non-receiving
ART patients (38.3 %) and bacterial pneumonia in the ART group (47.5 %). Segmental or
lobar air-space consolidations were the typical radiographic finding for bacterial pneumonia
in both groups. However, about one-third of ART-treated patients with bacterial pneumonia
disclosed interstitial pulmonary opacity with significant difference (p=0.040). Cavitary
lesions were observed only in non-ART group with bacterial pneumonia.
Conclusion: In HIV-infected patients with bacterial pneumonia, pulmonary interstitial
opacities are more frequently found in the patients receiving ART whereas the cavitary
lesions are solely demonstrated in the patients not receiving ART. No significant difference
in radiographic manifestation of other HIV-related pulmonary diseases regardless of
antiretroviral therapy.
Introduction
The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome
(AIDS) are global healthcare problem. In 2012, there were approximately 35 million people
worldwide suffering from HIV infection and its related diseases and also responsible for
death about 1.4-1.9 million people per year (1). There were new HIV infected patients
approximately 1.9-2.7 million peoples per year globally and in Thailand, an estimated
450,000 people were living with HIV in 2014 (1, 2).
Nowadays, HIV infection can be effectively managed with antiretroviral therapy
(ART). After incoming of ART since 1996, HIV infected patients have longer life
expectancy, dramatically decreased prevalence of opportunistic infection and mortality rate
(3-5)
. However even in the ART era, many HIV-infected patients still have HIV-related
diseases due to noncompliance, medication treatment failure or absence of medication
assessment (6).
Among HIV-related diseases, the respiratory tract has been one of most frequently
affected by the disease and up to 70% of HIV patients have at least one pulmonary
complication during the evolution of the disease (7, 8). Pulmonary complications in HIV
patients can be either infectious or non-infectious diseases. Generally, the approach to the
diagnosis of pulmonary diseases includes the clinical history, physical examination, CD4
count, imaging studies and specific diagnostic tests. Plain chest radiograph is an appropriate
initial imaging for diagnostic evaluation while chest computed tomography (CT) is more
sensitive to detect subtle findings and gives more imaging details. Imaging recognition
patterns can assist in the initial diagnosis and also narrow differential diagnosis. Many studies
have been proposed the imaging findings of HIV-related pulmonary diseases in the pre-ART
era. On the contrary, only a few studies have been reported about imaging findings in the
post-ART era.
The objective of this study is to evaluate chest imaging findings in HIV-related
pulmonary diseases presenting with chest symptoms between patients receiving and nonreceiving anti-retroviral therapy.
Materials and methods
Patients and radiological evaluation
After institutional review board approval (No: RAD-2558-03538), this retrospective
study obtained data from 180 HIV infected patients who had chest symptoms (cough,
dyspnea and hemoptysis) and subsequently underwent chest radiograph or chest CT in
Maharaj Nakorn ChiangMai hospital from August 2010 to August 2015. All of the patients
have been diagnosed of HIV-related pulmonary diseases which confirmed by laboratory
investigations, cytology, pathology or improvement of clinical or imaging after treatment. Six
patients were excluded due to no available radiographic imaging. Therefore, the study
population consisted of 174 patients. Patient characteristics including age and gender, clinical
presentations, CD4 lymphocyte count, assessment and compliance of ART, HIV-related
pulmonary diseases and radiologic findings were extracted from medical recording system
(Digicard) and CMU-PACS.
The chest radiographs and chest CT of the study population were reviewed by
consensus of two experienced radiologists (7 and 15 years of experience in cardiothoracic
radiology) and a third year radiology resident. All reviewers were blinded with regard to the
clinical presentation, diagnosis of HIV-related diseases and ART status. Presence and
character of opacities, nodules, cavities, pleural effusion, pneumothorax and adenopathy were
documented in each patient. Lymph nodes were considered enlarged if they had short axis
diameter greater than 1 cm. The locations of pulmonary opacities were recorded as diffuse or
focal distribution which specified by dividing of the lungs into three zones (upper, middle
and lower lung zones).
Pulmonary opacities were classified as alveolar pattern, interstitial pattern or groundglass pattern. Alveolar or airspace patterns were documented if they displayed an infiltration
with indistinct margin (Figure 1). Interstitial patterns were linear, reticular or reticulonodular
opacities with well demarcated margin (Figure 2). Ground-glass patterns were defined as
areas of haziness with preserved intervening bronchovascular margins (Figure 3).
The PA and AP chest radiographs were performed with Shimadzu R-20J (Shimadzu,
Tokyo, Japan). Portable chest radiographs were performed with mobile computed
radiography Mobilett Plus HP (Siemen, Erlangen, Germany). The chest CT scans were
performed by using multidetector CT scanners 64 slices MDCT scan Somatom definition
(Siemens, Erlangen, Germany) or 16 slices MDCT scan Aquilion (Toshiba, Tochigi-ken,
Japan). The slice thickness was 1 mm and the interval was 0.6 mm, each. Soft copy DICOM
images were evaluated with synapse software workstation version 4.1.
Statistical analysis
The continuous data were reported as mean ± standard deviation (SD) or Median ± iqr
depended on data distribution. The categorical data were reported as frequency and percent.
Fisher exact test was used for comparing the categorical data between two groups and student
t-test or Wilcoxon ranksum test was used for comparing the continuous data depending on
data distribution. P-value of less than 0.05 was indicated as statistically significant difference.
All statistical analyses were performed by using STATA program version 12.0.
Results
Of the 174 HIV-infected patients in this study, 59 (33.9%) had been received ART
with good compliance and 115 (66.1%) were non-receiving ART patients. Among the 59
patients receiving ART, 40 (67.8%) were men and 19 (32.2) were women. The ages ranged
from 11-82 years and the mean age was about 44.4 years. Of the 115 non-receiving ART
patients, there were 83 (72.2%) men and 32 (27.8%) women and the ages ranged from 6-67
years with 39.0 years of mean age. The median CD4 lymphocyte count was statistically
significant higher in patients receiving ART (226 cell/mm3; p<0.001). These data were
summarized in Table 1.
Most of the HIV-infected patients had infectious diseases (93.7%). Pneumocystis
jiroveci pneumonia (PCP) was the most common disease in non-receiving ART patients (38.3
%; p <0.001) whereas bacterial pneumonia was the most diagnosis in the ART group (47.5%;
p=0.002). Pulmonary tuberculosis was also commonly found in both the patients receiving
ART (22.0%) and not receiving ART (24.4%) without statistically significant difference.
Primary lung cancer was only found in the patient receiving ART. The other HIV-related
diseases were noticed in a small number and there was no statistically significant difference
between ART-treated patients and non-ART-treated patients. Pulmonary disease in HIVinfected patients between both groups were demonstrated in Table 2.
The relationships between chest radiographic findings of each common HIV-related
pulmonary disease and the status of anti-retroviral therapy were summarized in Table 3.
All of the PCP patients had pulmonary opacities and the most common opacity were
ground-glass pattern (Figure 4) in both ART group and non-ART group without statistical
significance. Diffuse distribution of the pulmonary opacities were also the most frequent
location in both groups. Cavitary lesions and pleural effusion were found in minority cases
(4.6%) of PCP patients not received ART. No pulmonary nodule was detected in all of the
PCP patients.
Pulmonary opacities were the most common findings depicted in bacterial pneumonia
in both the ART group (96.4%) and non-ART group (81.5%) (p=0.030). In details, we found
that interstitial pattern (Figure 5) was the statistically significant different parameter between
both groups of bacterial pneumonia (p=0.040). Diffuse pulmonary distribution were the most
documented location; however, no significant difference of the pulmonary location between
both groups was demonstrated (p=0.858). Cavitary lesions (Figure 6) were observed only in
the non-ART group with bacterial pneumonia (22.2%, p=0.010).
Pulmonary opacities in tuberculosis were found just about the same in every pattern in
either patient receiving ART or patient not receiving ART. Upper lung zone (Figure 7) was
the most common location in both groups. There were no statistically significant difference of
any radiographic finding between ART receiving patents and non-ART receiving patients
with tuberculosis.
Discussion
Since 1996, highly active antiretroviral therapy has been introduced to the HIVinfected patients, resulting in drastic reduction of opportunistic infections and mortality rate
(3-5)
. Even through in the ART era, many HIV-infected patients, especially in resource-limited
countries such as Thailand, still have HIV-related diseases due to absence of medication
assessment, noncompliance or medication treatment failure (6).
Among HIV-related diseases, the pulmonary system has been the most commonly
involved and pulmonary infections including tuberculosis, PCP and bacterial pneumonia
account for the majority of the HIV-related diseases (7-9). The relative incidence of bacterial
pneumonia has been increased replacing the PCP as the most frequently cause of HIV-related
pulmonary infection in the post-ART era (10). Our study also supports the aforementioned
point of view. From the result exhibited in Table 2, we found that bacterial pneumonia was
the most common disease in the ART-treated group whereas PCP was still the most
frequently HIV-related pulmonary disease in non-ART receiving group with statistically
significant difference. Because ART has had a substantial influence on viral load and CD4
lymphocyte level, most of the HIV-related patients receiving ART with good compliance
should have higher level of CD4 count as compared to the non-ART receiving patients (11).
Our study also showed the result supporting this point that the median CD4 lymphocyte count
was statistically significant higher in patients receiving ART (226 cell/mm3; p<0.001). The
CD4 lymphocyte level represents the degree of the immune status which is the potential risk
in developing of each infection (7, 11, 12). In this regard, a CD4 level above 200 cells/mm3
increases risk for bacterial pneumonia or tuberculosis while a CD4 level below 200 cells/mm3
tends to develop PCP, disseminated tuberculosis or other virulent opportunistic infections.
The accurate diagnosis of HIV-related pulmonary diseases is strongly influenced by
clinical history, laboratory data and radiographic findings. A confident radiographic diagnosis
can lead to administration of the proper empirical treatment and may also prevent the need
for other invasive procedures.
Segmental or lobar air-space consolidation is the typical radiographic finding for
bacterial pneumonia in either HIV-infected patients or non-HIV-infected patients (7). Our
study revealed that air-space patterns were documented the most common pulmonary opacity
in both HIV-infected receiving and not receiving ART patients. Nevertheless, about one-third
of ART-treated patients with bacterial pneumonia disclosed interstitial pulmonary opacity
(32.1%, p=0.040). In general, interstitial pulmonary infiltrations are the character of viral
pneumonia, however; some previous studies have been proposed that diffuse bilateral
interstitial opacities can be the manifestations of bacterial pneumonia, especially
Haemophilus infuenzae (up to 50%) (7, 13). Mycoplasma pneumoniae and Chlamydia
pneumoniae can also manifest with bilateral interstitial patterns even appear to be relatively
uncommon in HIV-infected patients (7). As mentioned earlier, the HIV-infected patients
receiving ART had significantly better immune status and we assumed that the incidence of
bacterial pneumonia in these patients should be similar to the non-HIV infected population;
therefore interstitial bacterial pneumonia patterns such as Haemophilus infuenzae,
Mycoplasma pneumoniae and Chlamydia pneumoniae may be commonly found in the ARTtreated patients as comparable to the non-ART-treated patients.
Pulmonary cavity is defined as an air-filled space within either a mass, nodule or area
of consolidation with or without containing fluid (14). A previous study reported that 85% of
HIV-infected cases with cavitary lesion were bacterial in etiology and the most frequently
organisms were Staphylococcus aureus and Pseudomonas aeruginosa (15). In our study, we
observed cavitary lesions due to bacterial pneumonia only in the non-ART group (22.2%,
p=0.010). This results could be due to the effects of advanced immune suppression in the
non-ART receiving patients. Bacterial pneumonia in AIDS has a tendency to develop
significant complications such as bacteremia, septic emboli and cavitary abscess, especially
in S. aureus and P. aeruginosa infection. Moreover, several studies have been reported some
unusual pathogens including Nocardia asteroides and Rhodococcus equi which can produce
cavitary lesions in severely immunocompromised HIV-infected patients (CD4 count < 200
cell/mm3) (12, 14, 16).
The results of this study come from a univariate statistical analysis because of small
population size; there will be some confounders influenced the diagnosis of each HIV-related
pulmonary disease. Another limitation of our study is that evaluation of HIV-related
pulmonary diseases based on only imaging findings without including the clinical
manifestations or laboratory results. Other limitations of this study include retrospective
review of medical records and imaging interpretations by consensus reading without
interobserver variability assessment.
Conclusion
In HIV-infected patients with bacterial pneumonia, pulmonary interstitial opacities are
more frequently found in the patients receiving ART whereas the cavitary lesions are solely
demonstrated in the patients not receiving ART. No significant difference in radiographic
manifestation of other HIV-related pulmonary diseases regardless of antiretroviral therapy.
References
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Report on the Global AIDS Epidemic. 2013.
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Joint United N, Programme, on HIV/AIDS, (UNAIDS) HIV and AIDS estimates
(2014). Available from: http://www.unaids.org/en/regionscountries/countries/thailand.
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disease in patients with HIV infection on antiretroviral therapy. AIDS. 2006;20(8):1095-107.
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diseases associated with HIV infection in the era of antiretroviral therapy: clinical and
imaging findings. Radiographics. 2014;34(4):895-911.
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Benito N, Moreno A, Miro JM, Torres A. Pulmonary infections in HIV-infected
patients: an update in the 21st century. Eur Respir J. 2012;39(3):730-45.
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Miller R. HIV-associated respiratory diseases. Lancet. 1996;348(9023):307-12.
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Boiselle PM, Tocino I, Hooley RJ, Pumerantz AS, Selwyn PA, Neklesa VP, et al.
Chest radiograph interpretation of Pneumocystis carinii pneumonia, bacterial pneumonia, and
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mimics. J Thorac Imaging. 1997;12(1):47-53.
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Gallant JE, Ko AH. Cavitary pulmonary lesions in patients infected with human
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Aviram G, Fishman JE, Sagar M. Cavitary lung disease in AIDS: etiologies and
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Table 1: Patient characteristics compared between untreated and treated-HIV patients
Mean age (year) ± SD
Treated-HIV group
N = 59
Untreated-HIV group
N = 115
44.4 ± 14.9
39.0 ± 11.9
p-value
0.599
Gender, N(%)
Female
Male
19 (32.2)
32 (27.8)
40 (67.8)
83 (72.2)
226 ± 245 (1,124)
33 ± 85 (1,954)
3
CD4 count (cells/ mm )
Median ± IQR (min-max)
<0.001
Table 2: Pulmonary diseases in HIV-infected patients between both groups
Treated-HIV group
N = 59
Untreated-HIV group
N = 115
p-value
Pulmonary tuberculosis
13 (22.0)
28 (24.4)
0.851
Pneumocystis jirovecii
pneumonia (PCP)
7 (11.9)
44 (38.3)
< 0.001
Bacterial pneumonia
28 (47.5)
27 (23.5)
0.002
Fungal infection
4 (6.8)
9 (7.8)
1.000
Non-tuberculous
mycobacterial infection
1 (1.7)
2 (1.7)
1.000
Lung cancer
4 (6.8)
0
-
Lymphoma
1 (1.7)
4 (3.5)
0.663
Kaposi sarcoma
1 (1.7)
1 (0.9)
1.000
Diseases
Table 3: The relationships between chest radiographic findings of each common HIV-related
pulmonary disease and the status of anti-retroviral therapy
Treated-HIV group
Untreated-HIV group
p-value
9 (69.2)
3 (23.1)
0
7 (25.0)
19 (67.9)
9 (32.1)
3 (10.7)
6 (46.2)
0.533
3 (33.3)
5 (55.6)
1 (11.1)
0
5 (38.5)
1 (7.7)
1 (7.7)
2 (15.4)
4 (21.1)
14 (73.7)
1 (5.3)
0
6 (21.4)
5 (17.9)
8 (28.6)
6 (21.4)
Pulmonary tuberculosis
Opacity, N (%)
Patchy
GGO
Interstitial
Predominant lobe
Diffuse
Upper lobe
Middle lobe
Lower lobe
Nodule
Adenopathy
Cavitary lesion
Pleural effusion
0.544
0.408
0.645
0.228
1.000
Pneumocystis jiroveci pneumonia (PCP)
Opacity
Patchy
GGO
Interstitial
Predominant lobe
Diffuse
Upper lobe
Middle lobe
Lower lobe
Nodule
Adenopathy
Cavitary lesion
Pleural effusion
7 (100)
0
5 (71.4)
2 (28.6)
44 (100)
9 (20.5)
30 (68.2)
5 (11.4)
4 (57.1)
1 (14.3)
0
2 (28.6)
0
1 (14.3)
0
0
35 (79.6)
3 (6.8)
0
6 (13.6)
0
5 (2.3)
2 (4.6)
2 (4.6)
27 (96.4)
15 (53.6)
3 (10.7)
9 (32.1)
22 (81.5)
19 (70.4)
1 (3.7)
2 (7.4)
11 (40.7)
3 (11.1)
3 (11.1)
10 (37.0)
4 (14.3)
1 (3.6)
0
8 (28.6)
11 (50.0)
1 (4.6)
2 (9.1)
8 (36.4)
3 (11.1)
3 (11.1)
6 (22.2)
5 (18.5)
0.299
0.231
0.258
1.000
1.000
Bacterial pneumonia
Opacity
Patchy
GGO
Interstitial
Predominant lobe
Diffuse
Upper lobe
Middle lobe
Lower lobe
Nodule
Adenopathy
Cavitary lesion
Pleural effusion
0.030
0.269
0.611
0.040
0.858
1.000
0.352
0.010
0.528
Figure 1
A 29-year-old man with AIDS (on ARV). He presents with progressive dyspnea.
The chest radiograph shows alveolar infiltration involving nearly entire the left
lung. The sputum culture shows mixed bacterial organism.
Figure 2
A 52-year-old man with AIDS (on ARV). He presents with cough and
progressive dyspnea. The chest radiograph shows reticular opacities in bilateral
middle to lower lung fields. Small amount of right pleural effusion is also noted
(arrow). After empirical antibiotics administration, the clinical was improved.
Figure 3
Pneumocystis jiroveci pneumonia in a 31-year-old man with AIDS (on ARV).
He presents with progressive dyspnea. The chest radiograph shows diffuse
ground grass opacities in bilateral lungs.
Figure 4
Pneumocystis jiroveci pneumonia in a 26-year-old man with AIDS (no ARV)
who developed progressive dyspnea. Chest radiograph reveals diffuse bilateral
ground grass opacities.
Figure 5
A 41-year-old man with AIDS (on ARV). He presents with fever and
dyspnea. Chest radiograph shows diffuse bilateral coarse reticular opacities.
After empirical antibiotics administration, the clinical was improved.
Figure 6
A 42-year-old woman with AIDS (no ARV).
She presents with severe sepsis and
hemoculture shows salmonellar septicemia.
The chest radiograph (right) shows a cavity in
left middle lung field (arrow). Contrastenhanced chest CT (left) on 2 weeks later
shows multiple cavities in both lungs.
Figure 7
A 42-year-old man with AIDS (no ARV). He presents with chronic cough. PA
chest radiograph shows reticular opacity predominately involving both upper
lobes. The sputum culture show Mycobacterium tuberculosis.