Chronic obstructive pulmonary disease in adults with human immunodeficiency virus infection: a systematic review

doi:10.4236/health.2011.34039

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Vol.3, No.4, 218-227 (2011) Health

doi:10.4236/health.2011.34039

Chronic obstructive pulmonary disease in adults with

human immunodeficiency virus infection: a systematic

review

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.

ABSTRACT

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

1. INTRODUCTION

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

219219

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. METHODS

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

HIV-infection.

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

COPD

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

[23,24].

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

Analysis

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

220

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

described

9) Antiretroviral treatment was described as standard,

at least three antiretroviral agents from at least two

different classes of medications, or otherwise, if

applicable.

3. RESULTS

3.1. Search Results and Study

Characteristics

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

221221

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

(yrs)

(range or

SD)

African

Americans %IDU %MSM %Current

Smokers %

Ever

Smokers %

History

of PCP

and

Bacterial

pneumonia

Recruited

from

Crothers-2005

(28) 881 34 50.3

(33-65) 18,45 9.9 38 63.3 NA 8.1

Veterans

outpatients

Crothers-2006

(12) 1014 100 50

(43-55) 58 31 NA 46 NA 10.9

Veterans

outpatients

Morris-2009

(9) 42 87 46.5

(32-69) 48.25 NA NA 42.1 97 15.5

Outpatients

HIV

clinic

George-2009

(32) 234 82 44.1

(26-70) 28.2 12 48 37.1 75 43.2

Outpatients

HIV

clinic

Gui-2010

(30) 119 79 43

(8.3) 19 25 NA 52 85 39

Outpatients

HIV

clinic

*Crothers-2010

(29) 33420 98 45

(39-51) 43 23 NA NA 80 12.8

Veterans

medical

outpatients

Drummond-2010

(33) 288 63.1 48.2

(43-53) 96.7 55.4 40 83.3 76.1 1.3

Commu

nity HIV

and IDU

Gingo-2010

(31) 167 73.6 46

(20-70) 49.7 18.6 49.7 52.7 59.7 44.3

STD

outpatie

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

222

Table 2. Assessment of the characteristics of HIV infection in the reports evaluating the prevalence of COPD in adults with HIV

infection.

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

On HAART %

Crothers-2005

(28)

Crothers

(2005)

345

(2 - 1880)

2.6

(1.6 - 5.9) 28

Crothers-2006

(12)

Crothers

(2006)

322

(225 - 544)

3.15

(1.7 - 4.4) 31.3

Morris-2009

(9)

Morris

(2009)

456

(4 - 1059)

3.9

(0.50 - 22.2) 78.6

George-2009

(32)

George

(2009)

371

(3 - 1368)

6.5

(2.8) 83.3

Gui-2010

(30)

Cui

(2010)

484

(274)

3.38

(1.26) 84

Crothers-2010

(29)

Crothers

2010

264

(108 - 451)

4.1

(3 - 4.93) 65

Drummond-2010

(33)

Drummond

(2010)

314

(177 - 503)

3.99

(0.5 - 26.7) 53.8

Gingo-2010

(31)

Gingo

(2010)

479

(22 - 1390)

3.89

(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.

First

author-year

(Reference)

Type of

study-name

Females were

excluded

Subjects with

cough, SOB*

or fever in the

Last month

were excluded

Subjects with

Missing data on

smoking, illegal

drug use were

excluded

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

Crothers-2005

(28)

Prospective

observational-

VA C S - 3

– – √ √ –

Crothers-2006

(12)

Prospective

observational-

VA C S - 5

√ – √ √ –

Morris-2009

(9)

Prospective

observational – √ NA NA NA

George-2009

(32)

Cross

sectional

survey

– √ NA √ √

Gui-2010

(30)

Cross

sectional

survey

– – NA NA NA

Crothers-2010

(29)

Prospective

observational-

VACS-VC

– – √ NA –

Drummond-2010

(33)

Prospective

observational-

ALIVE

– – √ NA –

Gingo-2010

(31)

Cross

sectional

survey

– √ 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

223223

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

(Reference)

Consecutive

patients

were

enrolled

Recruitment

period was

Follow-up

period was

defined

Subjects lost

to follow-up

were

described

Subjects

known to be

alive but lost

to follow-up

< 10%

Respiratory

symptoms

assessed with a

standardized

questionnaire

Collection of

data: interview

and

standardized

Collection of

data: survey and

standardized

medical records

Crothers-2005

(28) √ √ √ √ √ √ NA √

Crothers-2006

(12) √ √ √ √ √ √ NA √

Morris-2009

(9) √ – – – – – √ NA

George-2009

(32) √ √ NA NA NA √ √ NA

Gui-2010

(30) √ – NA NA NA √ NA √

Crothers-2010

(29) √ √ √ √ √ √ NA √

Drummond-2010

(33) √ √ √ √ – √ √ NA

Gingo-2010

(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

224

Table 5. Assessment of respiratory symptoms, method to evaluate the prevalence and prevalence of COPD in adults with HIV-

infection.

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 %

Crothers-2005

(28) 35 ICD-9 codes 10.36

Crothers-2006

(12) NA Patient self report

ICD-9 1510

Morris-2009

(9) 21 Post-bronchodilator

FEV1/FVC < 0.7 35

George-2009

(32) 31 FEV1/FVC

below the 5% lower limit of

normal adjusted for age 8.6

Gui-2010

(30) 42.8 Post-bronchodilator

FEV1/FVC < 0.7 4

Crothers-2010

(29) – ICD-9 codes 16

Drummond-2010

(33) 48.5 Pre-bronchodilator

FEV1/FVC < 0.7 15.6

Gingo-2010

(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%

[33].

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

225225

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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