Vol.3, No.4, 218-227 (2011) Health
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Chronic obstructive pulmonary disease in adults with
human immunodeficiency virus infection: a systematic
Elpis Giantsou1,2*, Duncan Powrie2
1Acute Medical Unit, Southend University Hospital, Essex, England; *Corresponding Author: elpisgiantsou@yahoo.com;
2Heart and Chest Clinic, Southend University Hospital
Received 29 January 2011; revised 20 February 2011; accepted 23 March 2011.
Objective: To determine the prevalence of chro-
nic obstructive pulmonary disease (COPD) in
adults with Human Immunodeficiency virus in-
fection (HIV). Design: Systematic review of
Medline, Embase, CINAHL, PsycINFO and ref-
erences from identified papers. Study selection:
Studies determining the prevalence of COPD in
adults with HIV infection. Independent duplicate
data extraction. Study quality was assessed in
terms of whether consecutive patients were en-
rolled, recruitment and follow-up periods were
defined, <10% of subjects were lost to follow-up,
subjects with missing data, method of COPD
diagnosis and antiretroviral treatment were de-
scribed. Data synthesis and results: Of the 911
citations identified, 8 North American studies
conducted from 2005 to 2010 were reviewed.
The demographics were: mean age 43 - 50.3yrs,
>60% males, <50% African Americans, 37.1% -
83.3% active smokers, >60% on antiretroviral
therapy. COPD was diagnosed by post-bron-
chodilator FEV1/FVC < 0.7 in three studies, by
International Classification of Diseases (ICD-9)
codes in three studies, by FEV1/FVC < 5% of
lower adjusted normal in one and by pre-
bronchodilator FEV1/FVC < 0.7 in another study.
The prevalence was 10% - 35%, except for one
study that recorded prevalence of 4% by post-
bronchodilator FEV1/FVC < 0.7, but <38% of
patients with prebronchodilator FEV1/FVC < 0.7
had post-bronchodilator spirometry in that
study. Conclusion: COPD is becoming increas-
ingly common in HIV infected as they smoke
and live longer due to efficient antiretrovirals.
However, definite conclusions cannot be drawn
and more longitudinal studies are needed. In the
meantime health care providers should be vigi-
lant to screen for undiagnosed COPD and hesi-
tant to attribute respiratory symptoms solely to
HIV infection.
Keywords: HIV, COPD; Systematic Review
Effective antiretroviral therapies have improved the
prognosis for patients infected with the Human Immu-
nodeficiency Virus (HIV) [1]. The Collaborations in
HIV Research–US (CHORUS ) cohort study reported a
median survival of 20.4 years for HIV positive subjects,
with mean age at death 60.4yrs and cause of death not
directly attributable to HIV in 41% [2]. Therefore in the
era of Highly Active Antiretroviral Therapy (HAART)
patients with HIV infection live longer and experience
increased mortality from causes not directly attributable
to HIV. Recent data suggest that Chronic Obstructive
Pulmonary disease (COPD) is becoming increasingly
common in HIV-infected patients on antiretrovirals [3].
However even studies conducted before the introduction
of HAART suggested that HIV infected patients have
increased susceptibility to COPD. Diaz et al reported
that the prevalence of emphysema in 114 HIV infected
patients was 15% compared to only 2% in 44 HIV nega-
tive patients [4]. Poirier et al reported that the prevalence
of airway hyperresponsiveness was 30.1% in 151 HIV
positive smokers compared to 13.3% in 82 HIV negative
smokers [5]. As bronchial hyperresponsiveness can be a
potential risk factor for progressive COPD in smokers,
the data by Poirier et al may indicate a potential link
between smoking and HIV infection that could acceler-
ate the development of COPD [6]. The fact that 40-70%
of HIV positive subjects smoke in the era of HAART
should probably also be considered [7]. The rate of in-
fectious pulmonary complications has been reduced
withthe new antiretrovirals [8]. However, Morris et al
E. Giantsou et al. / Health 3 (2011) 218-227
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suggested that, colonization with Pneumocystis jirovecii
can predict lower FEV1 and FEV1/FVC, as well as
clinical airway obstruction without having necessarily
clinical evidence for chest infection [9]. These investi-
gators reported that the presence of Pneumocystis in the
lungs even at low levels in clinically healthy HIV posi-
tive subjects can produce inflammatory changes similar
to those seen in COPD independant of smoking. This
observation lend support to the hypothesis that Pneumo-
cystis can be involved in the progression of airway ob-
struction in HIV infected [10]. Recent reports suggested
that HIVinfection may be an independant risk factor for
COPD [11,12].
The prevalence of COPD in HIV infected subjects has
important clinical and policy implications for future de-
livery of care. Although previously assessed it has yet to
be summarized in a systematic review. The purpose of
this review is to systematically retrieve and appraise the
available data on the prevalence of COPD in patients
with HIV-infection.
2.1. Search Strategy
The review followed the methodology of systematic re-
views [13,14,15]. Two researchers independently searched
the literature by using the Ovid search platform of CI-
NAHL (1981 to October 2010), EMBASE (1980 to Oc-
tober 2010), Medline (1950 to October 2010) and Psy-
chINFO (1967 to January 2010) databases. The follow-
ing search terms were identified through the Medical
Subject Headings dictionary [16]: HIV, COPD, Chronic
Obstructive Pulmonary Disease, Chronic Obstructive
Lung Disease, Chronic Airflow Obstruction, Chronic ir-
reversible airflow obstruction, Chronic Bronchitis, Em-
physema. All different possible combinations of terms
were used in the literature searches to maximize refer-
ences retrieved. The library of the Cochrane reviews was
consulted to verify whether a given review has already
been made [17]. A hand search was also performed of
reference lists of the relevant review articles and of the
articles identified at the electronic search regardless of
the initial publication language. Annals of relevant con-
gresses were reviewed searching for presented but not
published studies.
2.2. Eligibilty Criteria
Potentially relevant studies were identified by title, then
by abstract, then by full text. Studies were selected for
review if they met the three following inclusion criteria:
1) Adults (> 16 years old)
2) HIV infection as defined by the World Health Or-
ganization [18] and
3) COPD documented in patients diagnosed with
All retrieved reports were checked for inclusion crite-
ria in a blinded fashion by two authors. In the case of
duplicate publication the largest study, if applicable was
included. Any disagreement between the investigators was
solved independently by a third experienced reviewer.
2.3. Exclusion Criteria
Studies were excluded first by title, then by abstract and
finally by full text if they were:
1) Case reports. Studies with small samples have a
greater chance of publication bias [19]
2) Narrative pieces without data to support observa-
tions (editorials, policy recommendations, opinion
surveys and commentaries)
3) Enrolling patients with HIV exclusively from hos-
pital inpatient wards. The rate of COPD in hospital
inpatients may be biased upwards compared to pa-
tients at a similar stage of disease who were not
hospitalized. Hospital inpatients may have faster
rates at which they develop Acquired Immune De-
ficiency Syndrome and therefore susceptibility to
comorbidities, including COPD [20].
4) Using International Codes for Disease classifica-
tion (ICD-9 codes) to diagnose COPD without
provision to improve the accuracy of this source of
data by including inpatient codes at least once and
outpatient codes at least twice [21].
2.4. Description of Methods to Diagnose
Criteria of COPD diagnosis are as following:
1) British Thoracic Society: FEV 1 /FVC < 0.70 and
if FEV 1 > 80% of predicted, presence of symp-
toms like cough and dyspnea [22].
2) European Respiratory Society/American Thoracic
Society: post-bronchodilator FEV1/FVC < 0.70
3) Global Initiative for Obstructive Lung Disease:
post-bronchodilator FEV1/FVC < 0.70 [25].
For the use of ICD-9 codes to diagnose COPD the
relevant guideline suggests that the code is to be used
when the medical record documentation substantiates
obstructive lung disease including among other tests
spirometry according the ATS protocol [26].
2.5. Data Extraction, Synthesis and
For each eligible study data were extracted on number
of patients included, gender, age, race or ethnicity of
E. Giantsou et al. / Health 3 (2011) 218-227
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participants, intravenous drug abuse, men who have sex
with men, smoking status, history of Pneumocystis carinii
or bacterial pneumonia, source of recruitment, CD4 and
HIV viral load levels, treatment with HAART, study de-
sign and key exclusion criteria, study quality and inclu-
sion criteria, method use to diagnose COPD and respira-
tory symptoms. Outcome assessed was the prevalence of
COPD. Data extraction was performed by one author
and cross-checked against extraction by another reviewer.
Due to qualitative and quantitative heterogeneity in
patients diagnosed with HIV infection a quantitative
synthesis was not possible. A descriptive and qualitative
analysis was therefore undertaken.
The quality of eligible studies was assessed on the ba-
sis of the following features [27]:
1) consecutive patients were enrolled
2) the recruitment period was defined
3) the follow-up period was defined
4) subjects lost to follow-up were described
5) subjects known to be alive but lost to follow-up
were < 10%
6) respiratory symptoms were assessed with a stan-
dardized questionnaire
7) the method to assess clinical data was clearly de-
scribed (interview and standardized medical records
versus survey and standardized medical records)
8) management of subjects with missing data was
9) Antiretroviral treatment was described as standard,
at least three antiretroviral agents from at least two
different classes of medications, or otherwise, if
3.1. Search Results and Study
The flow chart of the search results is presented in
Figure 1. The search identified 911 citations from which
Figure 1. Flow chart of literature search results.
E. Giantsou et al. / Health 3 (2011) 218-227
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
836 abstracts and 75 full-text publications were retrieved.
A total of 8 non-interventional studies conducted in USA
during the period 2005-2010 were eligible for review.
The characteristics of the patients included in the studies
assessing the prevalence of COPD in HIV infected pa-
tients are presented in Tables 1 and 2. Three studies
evaluated veterans outpatients [12,28,29], four evaluated
outpatients of HIV or Sexually Transmitted Disease
clinics [9,30-32], one evaluated intravenous drug users
recruited from the community [33]. Five studies were
prospective observational in design and three cross sec-
tional surveys. The mean age of patients ranged from 43
to 50.3 yrs. The age range was 32 to 70yrs, but in four
out of eight studies it was 39-55 yrs. Men were more
than 60% of the population in all but one study. African
Americans were less than 50% of the population in all
but two studies. Illicit drug use was reported in up to
25% of the population in all but two studies. Men who
have sex with men ranged from 38% to 49.7%. The
prevalence of active smoking ranged from 37.1% to
83.3% and in four out of eight studies it was above 50%.
History of previous Pneumocystis or bacterial pneumo-
nia ranged from 1.3% to 44.3% although in six out of
eight studies ranged from 5% to 15.5%. The mean CD4
varied from 264 cells.mm3 to 484 cells.mm3. The mean
HIV viral load was from 2.6 to 6.5 copies per ml. In five
out of eight studies more than 60% of the population was
on HAART although the proportion of patients on
HAART ranged from 28% to 83.3%. In three of the five
prospective observational studies the period of time from
diagnosis of HIV infection to diagnossis of COPD was
reported and it was 10. 33 yrs (mean) with range from 9
to 13yrs [30-32].
The design and exclusion criteria for the studies as-
sessing the prevalence of COPD in HIV infected patients
are presented in Table 3. Three studies excluded sub-
jects with cough, shortness of breath or fever in the last
month before study enrolment [9,31,32]. All studies
provided data on smoking and illicit drug use for every
subject included. This was so because four studies ex-
cluded subjects with missing data on smoking or illicit
drug use and the other four had no subjects with missing
Table 1. Characteristics of the studies assessing the prevalence of COPD in adults with HIV.
First author year HIV +
N, Men %
Mean age
(range or
Americans %IDU %MSM %Current
Smokers %
Smokers %
of PCP
(28) 881 34 50.3
(33-65) 18,45 9.9 38 63.3 NA 8.1
(12) 1014 100 50
(43-55) 58 31 NA 46 NA 10.9
(9) 42 87 46.5
(32-69) 48.25 NA NA 42.1 97 15.5
(32) 234 82 44.1
(26-70) 28.2 12 48 37.1 75 43.2
(30) 119 79 43
(8.3) 19 25 NA 52 85 39
(29) 33420 98 45
(39-51) 43 23 NA NA 80 12.8
(33) 288 63.1 48.2
(43-53) 96.7 55.4 40 83.3 76.1 1.3
nity HIV
and IDU
(31) 167 73.6 46
(20-70) 49.7 18.6 49.7 52.7 59.7 44.3
nts clinic
Abbreviations: COPD; Chronic obstructive pulmonary disease, HIV; Human immunodeficiency virus, MSM; Men who have sex with men, PCP; Pneumocystis
carinii pneumonia, STD; Sexually transmitted diseases, IDU; Intravenous drug users. *Data for this study are presented as they available so far on www. vaco-
hort.org, accessed 07/11/2010
E. Giantsou et al. / Health 3 (2011) 218-227
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Table 2. Assessment of the characteristics of HIV infection in the reports evaluating the prevalence of COPD in adults with HIV
First authoryear
(Reference) First author (year) Mean CD4 cells.mm3
(range or SD)
Mean Log10 HIV-RNA viral load
copies/ml (range or SD) at
diagnosis of COPD
(2 - 1880)
(1.6 - 5.9) 28
(225 - 544)
(1.7 - 4.4) 31.3
(4 - 1059)
(0.50 - 22.2) 78.6
(3 - 1368)
(2.8) 83.3
(1.26) 84
(108 - 451)
(3 - 4.93) 65
(177 - 503)
(0.5 - 26.7) 53.8
(22 - 1390)
(3.89 - 14.3) 80.7
Abbreviations: HIV; Human Immunodeficiency Virus, COPD; Chronic Obstructive Pulmonary Disease, HAART; Highly Active Antiretroviral Therapy
Table 3. Design and key exclusion criteria for studies assessing the prevalence of COPD in adults with HIV-infection.
Type of
Females were
Subjects with
cough, SOB*
or fever in the
Last month
were excluded
Subjects with
Missing data on
smoking, illegal
drug use were
Subjects without CD4
or HIV RNA levels
were excluded or
Comparisons with and
without subjects with
missing data found no
significant differences
Subjects reporting
antiretroviral other
than standard*
were excluded
VA C S - 3
– –
VA C S - 5
observational NA NA NA
– – NA NA NA
– – NA –
– – NA –
Abbreviations: COPD; Chronic obstructive pulmonary disease, HIV; Human immunodeficiency virus infection, SOB; Shortness of breath, NA; Non-ap-
plicable, as there are no missing data *At least three antiretroviral agents from at least two classes of medications.
E. Giantsou et al. / Health 3 (2011) 218-227
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data on smoking or illicit drugs. Similarly all studies
provided CD4 level and HIV viral load for every subject
included at the time of COPD diagnosis. This was so
because four studies excluded subjects without CD4 or
HIV viral load and the other four had no subjects with
missing data. In three studies the subjects were on stan-
dard antiretroviral therapy and one study excluded sub-
jects with other than standard antiretroviral therapy.
3.2. Quality Assessment
The quality assessment of the studies assessing the
prevalence of COPD in HIV infected subjects is pre-
sented in Table 4. All studies enrolled consecutive pa-
tients. The recruitment period was described in all but
two studies [9,30]. The follow-up period was defined in
four out of five prospective observational cohorts and it
was not applicable for the three cross sectional surveys.
Subjects lost to follow-up were fully described in four
studies whereas three more studies had no subjects lost
to follow-up. Of the four studies who had subjects lost to
follow-up but known to be alive at the time of the study
three confirmed that these subjects represented less than
10% of the population [11,12,29]. Respiratory symptoms
were assessed by a standardized respiratory questionnaire
in all but one study [9]. Data were obtained by interview
and standardized medical records in four out of eight
studies and by survey and standardized medical records
in the other four studies.
3.3. Assessment of Prevalence of COPD
The method used to diagnose COPD and the relevant
prevalence is presented in Table 5. In three studies
COPD was diagnosed with post-bronchodilator FEV1/
FVC < 0.7, in three studies with ICD-9 codes, in one
study with FEV1/FVC below the 5% lower limit of age
adjusted normal and in one study with pre-bronchodila-
tor FEV1/FVC < 0.7. The prevalence of COPD ranged
from 4% to 35%. The highest COPD prevalence of 35%
corresponded to clinically free from chest infection HIV
positive patients colonized with Pneumocystis [9]. In the
same study the prevalence of COPD for HIV positive
who were not colonized with Pneumocystis was less than
6%. In the study with the lowest recorded prevalence of
4%, obstructive lung function was diagnosed by pre-
bronchodilator FEV1/FVC < 0.7 in 12%, but only 38%
of them underwent post-bronchodilator spirometry [30].
In the same study logistic regression was used to dem-
onstrate that COPD was associated with increased odds
(OR = 2.25 CI: 1.43 to 3.54) of reporting MRC dyspnea
scale > 3 and that HIV was also associated with in-
creased odds (OR = 1.50 CI: 1.08-2.09) of reporting MRC
dyspnea scale > 2 [30]. Another four studies reported
prevalence between 10% and 16% [12,28,29,33]. One of
the studies using ICD-9 codes, reported prevalence of
COPD of 15% when patients were self reported to be
examined for COPD and 10% when ICD-9 codes were
used [12]. The respiratory symptoms in the 8 studies
Table 4. Assessment of quality of studies reporting the prevalence of COPD in adults with HIV-infection
First author-year
period was
period was
Subjects lost
to follow-up
known to be
alive but lost
to follow-up
< 10%
assessed with a
Collection of
data: interview
Collection of
data: survey and
medical records
(28) NA
(12) NA
(9) – – – – – NA
(32) NA NA NA NA
(30) – NA NA NA NA
(29) NA
(33) NA
(31) NA NA NA NA
Abbreviations: COPD; Chronic obstructive pulmonary disease; HIV; human immunodeficiency virus, NA; non applicable.
E. Giantsou et al. / Health 3 (2011) 218-227
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Table 5. Assessment of respiratory symptoms, method to evaluate the prevalence and prevalence of COPD in adults with HIV-
First author-year (Reference) Respiratory symptoms among
subjects included in the study %
Method to determine the
prevalence of COPD
Prevalence of COPD among all
subjects included in the study %
(28) 35 ICD-9 codes 10.36
(12) NA Patient self report
ICD-9 1510
(9) 21 Post-bronchodilator
FEV1/FVC < 0.7 35
(32) 31 FEV1/FVC
below the 5% lower limit of
normal adjusted for age 8.6
(30) 42.8 Post-bronchodilator
FEV1/FVC < 0.7 4
(29) ICD-9 codes 16
(33) 48.5 Pre-bronchodilator
FEV1/FVC < 0.7 15.6
(31) 63.5 Post-bronchodilator
FEV1/FVC < 0.7 21
Abbreviations: COPD; Chronic obstructive pulmonary disease, HIV; Human immunodeficiency virus.
included in this review ranged from 31% to 63%. In the
three studies which excluded patients with cough, short-
ness of breath or fever in the last month before enrol-
ment the respiratory symptoms ranged from 21% to 63%.
In three of the eight studies the respiratory symptoms
rate was > 40% [30-33].
Three studies compared the prevalence of COPD be-
tween HIV positive and HIV negative patients with simi-
lar characteristics [12,29,33]. Two of them adjusted for
known risk factors of COPD and found that HIV posi-
tive compared to HIV negative subjects were 50% more
likely to get diagnosed with COPD by ICD-9 codes (OR
= 1.47 with CI: 1.01 to 2.13) and 60% more likely to
have a diagnosis of COPD by self report (OR = 1.58, CI:
1.14 to 2.19). The third study found prevalence of COPD
of 15.7% in HIV positive and of 15.5% in HIV negative
subjects [ 33 ]. In that study the population was com-
posed entirely of intravenous drug users and intravenous
drug use is a well known risk factor for COPD [34]. The
same authors demonstrated that in HIV patients, in
whom the mental health summary score is already ad-
versely affected by HIV, the presence of COPD is asso-
ciated with 2.43 unit further decrease in the mental
health summary score, which can be translated to an
increase in the likelihood of death by approximately 8%
4. Discussion
With the efficacy of HAART, life expectancy of HIV
infected individuals has extended such that they are be-
coming increasingly susceptible to chronic debilitating
diseases like COPD. HIV positive subjects have reported
rates of respiratory symptoms comparable to those ob-
served in elderly smokers, they are diagnosed with COPD
at younger age and smoke more than the general popula-
tion. HIV and COPD have been reported to exert addi-
tive effects on dyspnea and reduction of quality of life.
Although no definite conclusion about the prevalence of
COPD in HIV can be drawn from the data available, as
the reported prevalence varies considerably, it is evident
that as HIV patients become an aging population, health
care providers should consider COPD when evaluating
HIV infected patients, especially those who present with
respiratory symptoms or impairment.
There are comparability issues that should be consid-
ered in the interpretation of our findings. To determine
the prevalence of COPD in HIV infected patients require
vigorous longitudinal studies. However the studies
available consisted of 5 prospective cohorts and 3 cross
sectional studies. Most research has been conducted in
North American tertiary care University centers in the
period 2009-2010. Therefore the recorded prevalence
may not reflect the situation in other continents or an-
other level of care. The majority of patients included
were male smokers that prevent us from drawing con-
clusions about the prevalence of COPD in HIV positive
females who have been reported to have high smoking
rates [34]. However although predominantly male the
cohorts included in our study were ethnically diverse.
The case mix varied between the studies since three of
them studied veterans, two studied intravenous drug
users and three outpatients with HIV. Although, the de-
E. Giantsou et al. / Health 3 (2011) 218-227
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mographics of the studies included in this review were
those of patients at risk for HIV and COPD, it could be
argued that our results may not necessarily reflect other
populations. However, the Veterans Health Care System
is the largest provider of healthcare to HIV infected in
USA and demographics similar to those included in our
review have been described in other studies of HIV-
infected non-veterans [35]. The method to diagnose HIV
was ICD-9 codes in three of the eight studies and spi-
rometry in the rest. It has been previously reported that
ICD-9 are more likely to underestimate than overesti-
mate the prevalence of chronic conditions and the au-
thors addressed this potential limitation by using a sec-
ond method to measure prevalence, the patient self- re-
port [12,36-38]. The consistency of the measured preva-
lence with these two methods strengthens the validity of
their results on prevalence with ICD-9 codes. Additional
strength to their findings is added by the fact that the
authors assessed the prevalence of COPD in HIV in-
fected compared to demographically matched HIV- un-
infected controls and found it to be 50% to 60% more
common. However, spirometry remains the gold stan-
dard for the diagnosis of COPD. The previously reported
effect of the use of pre-bronchodilator FEV1/FVC < 0.7
compared to post-bronchodilator FEV1/FVC < 0.7 on
the estimated prevalence of COPD should also probably
be considered [39].
The question whether HIV infected is at sufficient risk
to benefit from screening for COPD remains unanswered
from the available data. However the studies included in
this review have highlighted potential mechanisms who
may explain, at least in part, the pathogenesis of COPD
in HIV. Multiple interacting factors have been described.
HIV infected individuals demonstrate elevated systemic
and topical inflammatory cytokines, including those in-
volved in the pathogenesis of COPD [40-42]. Episodes
of clinical pneumonia and colonization with respiratory
organism may contribute to airway obstruction in sub-
jects with HIV infection [43,44]. Colonization with
Pneumocystis jirovecii, the organism that is associated
with human Pneumocystis Carinii pneumonia, has been
associated with the presence and severity of COPD in
HIV negative subjects [9]. Pneumocystis jirovecii has
been identified in the sputum of HIV positive smokers
compared to non-smokers in the absence of active PCP
[9]. HIV has been suggested to accelerate premature
frailty and aging related changes in the immune system
[45-48]. As a result HIV may render the lung more sus-
ceptible to diseases such as COPD, which has also been
suggested as a disease of accelerated lung aging [49,50].
Smoking, a habit highly prevalent in HIV population,
exacerbates cellular senescence [51]. We cannot but ob-
serve that from the suggested potential links between
HIV and COPD, smoking and infection-colonization may
be susceptible to interventions. Considering that there are
approximately 31.3 million adults who live with HIV
today and 2.3 million newly infected every year, who are
in their majority smokers with mean age at death 60yrs,
the relevant research should probably be considered as
money well spent [52].
In this systematic review we found that, although defi-
nite conclusion about the prevalence of COPD in HIV
cannot be drawn from the data available so far, COPD is
becoming increasingly common among HIV infected, as
they now smoke and live longer due to highly effective
antiretrovirals. We clearly need more longitudinal stud-
ies to assess the prevalence of COPD in HIV infected
and the potential links between the two. In the meantime
healthcare providers should be vigilant to screen for un-
diagnosed COPD and hesitant to attribute respiratory
symptoms solely to HIV infection.
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