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Helicobacter pylori Infection Is Associated with Higher CD4 T Cell Counts and Lower HIV-1 Viral Loads in ART-Naïve HIV-Positive Patients in Ghana

Identifieur interne : 000210 ( Pmc/Corpus ); précédent : 000209; suivant : 000211

Helicobacter pylori Infection Is Associated with Higher CD4 T Cell Counts and Lower HIV-1 Viral Loads in ART-Naïve HIV-Positive Patients in Ghana

Auteurs : Fred Stephen Sarfo ; Kirsten Alexandra Eberhardt ; Albert Dompreh ; Edmund Osei Kuffour ; Mareike Soltau ; Marei Schachscheider ; Jan Felix Drexler ; Anna Maria Eis-Hübinger ; Dieter H Ussinger ; Emelia Efua Oteng-Seifah ; George Bedu-Addo ; Richard Odame Phillips ; Betty Norman ; Gerd Burchard ; Torsten Feldt

Source :

RBID : PMC:4658036

Abstract

Background

Worldwide, there is a high co-endemicity of HIV and H. pylori infection and there is growing evidence that H. pylori co-infection is associated with parameters of HIV disease progression. The objective of this study was to investigate the prevalence of H. pylori infection, and the association with clinical, immunological and virological parameters in a large cohort of HIV-infected individuals and uninfected controls in a West African country.

Methods

HIV-patients (n = 1,095) and HIV-negative individuals (n = 107) were recruited at a university hospital in Ghana. H. pylori status was determined using stool antigen testing. HIV-related, clinical and socio-demographic parameters were recorded and analyzed according to H. pylori status.

Results

The prevalence of H. pylori infection was significantly lower in HIV-positive compared to HIV-negative individuals (51.5 vs. 88%, p<0.0001). In HIV patients, H. pylori prevalence decreased in parallel with CD4+ T cell counts. In ART-naïve HIV-infected individuals, but not in those taking ART, H. pylori infection was associated with higher CD4 cell counts (312 vs. 189 cells/μL, p<0.0001) and lower HIV-1 viral loads (4.92 vs. 5.21 log10 copies/mL, p = 0.006). The findings could not be explained by socio-demographic confounders or reported use of antibiotics. Having no access to tap water and higher CD4+ T cell counts were identified as risk factors for H. pylori infection.

Conclusions

H. pylori prevalence was inversely correlated with the degree of immunosuppression. In ART-naïve individuals, H. pylori infection is associated with favorable immunological and virological parameters. The underlying mechanisms for this association are unclear and warrant investigation.


Url:
DOI: 10.1371/journal.pone.0143388
PubMed: 26599971
PubMed Central: 4658036

Links to Exploration step

PMC:4658036

Le document en format XML

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<name sortKey="Oteng Seifah, Emelia Efua" sort="Oteng Seifah, Emelia Efua" uniqKey="Oteng Seifah E" first="Emelia Efua" last="Oteng-Seifah">Emelia Efua Oteng-Seifah</name>
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<name sortKey="Soltau, Mareike" sort="Soltau, Mareike" uniqKey="Soltau M" first="Mareike" last="Soltau">Mareike Soltau</name>
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<name sortKey="Schachscheider, Marei" sort="Schachscheider, Marei" uniqKey="Schachscheider M" first="Marei" last="Schachscheider">Marei Schachscheider</name>
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<name sortKey="Drexler, Jan Felix" sort="Drexler, Jan Felix" uniqKey="Drexler J" first="Jan Felix" last="Drexler">Jan Felix Drexler</name>
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<name sortKey="Eis Hubinger, Anna Maria" sort="Eis Hubinger, Anna Maria" uniqKey="Eis Hubinger A" first="Anna Maria" last="Eis-Hübinger">Anna Maria Eis-Hübinger</name>
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<name sortKey="H Ussinger, Dieter" sort="H Ussinger, Dieter" uniqKey="H Ussinger D" first="Dieter" last="H Ussinger">Dieter H Ussinger</name>
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<name sortKey="Oteng Seifah, Emelia Efua" sort="Oteng Seifah, Emelia Efua" uniqKey="Oteng Seifah E" first="Emelia Efua" last="Oteng-Seifah">Emelia Efua Oteng-Seifah</name>
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<addr-line>Kumasi Centre for Collaborative Research, Kumasi, Ghana</addr-line>
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<name sortKey="Bedu Addo, George" sort="Bedu Addo, George" uniqKey="Bedu Addo G" first="George" last="Bedu-Addo">George Bedu-Addo</name>
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<addr-line>Kwame Nkrumah University of Science and Technology, Kumasi, Ghana</addr-line>
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</nlm:aff>
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<addr-line>Komfo Anokye Teaching Hospital, Kumasi, Ghana</addr-line>
</nlm:aff>
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<name sortKey="Burchard, Gerd" sort="Burchard, Gerd" uniqKey="Burchard G" first="Gerd" last="Burchard">Gerd Burchard</name>
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<addr-line>Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany</addr-line>
</nlm:aff>
</affiliation>
</author>
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<name sortKey="Feldt, Torsten" sort="Feldt, Torsten" uniqKey="Feldt T" first="Torsten" last="Feldt">Torsten Feldt</name>
<affiliation>
<nlm:aff id="aff003">
<addr-line>Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff004">
<addr-line>Clinic of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, Germany</addr-line>
</nlm:aff>
</affiliation>
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<title level="j">PLoS ONE</title>
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<div type="abstract" xml:lang="en">
<sec id="sec001">
<title>Background</title>
<p>Worldwide, there is a high co-endemicity of HIV and
<italic>H</italic>
.
<italic>pylori</italic>
infection and there is growing evidence that
<italic>H</italic>
.
<italic>pylori</italic>
co-infection is associated with parameters of HIV disease progression. The objective of this study was to investigate the prevalence of
<italic>H</italic>
.
<italic>pylori</italic>
infection, and the association with clinical, immunological and virological parameters in a large cohort of HIV-infected individuals and uninfected controls in a West African country.</p>
</sec>
<sec id="sec002">
<title>Methods</title>
<p>HIV-patients (n = 1,095) and HIV-negative individuals (n = 107) were recruited at a university hospital in Ghana.
<italic>H</italic>
.
<italic>pylori</italic>
status was determined using stool antigen testing. HIV-related, clinical and socio-demographic parameters were recorded and analyzed according to
<italic>H</italic>
.
<italic>pylori</italic>
status.</p>
</sec>
<sec id="sec003">
<title>Results</title>
<p>The prevalence of
<italic>H</italic>
.
<italic>pylori</italic>
infection was significantly lower in HIV-positive compared to HIV-negative individuals (51.5 vs. 88%, p<0.0001). In HIV patients,
<italic>H</italic>
.
<italic>pylori</italic>
prevalence decreased in parallel with CD4+ T cell counts. In ART-naïve HIV-infected individuals, but not in those taking ART,
<italic>H</italic>
.
<italic>pylori</italic>
infection was associated with higher CD4 cell counts (312 vs. 189 cells/μL, p<0.0001) and lower HIV-1 viral loads (4.92 vs. 5.21 log10 copies/mL, p = 0.006). The findings could not be explained by socio-demographic confounders or reported use of antibiotics. Having no access to tap water and higher CD4+ T cell counts were identified as risk factors for
<italic>H</italic>
.
<italic>pylori</italic>
infection.</p>
</sec>
<sec id="sec004">
<title>Conclusions</title>
<p>
<italic>H</italic>
.
<italic>pylori</italic>
prevalence was inversely correlated with the degree of immunosuppression. In ART-naïve individuals,
<italic>H</italic>
.
<italic>pylori</italic>
infection is associated with favorable immunological and virological parameters. The underlying mechanisms for this association are unclear and warrant investigation.</p>
</sec>
</div>
</front>
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<journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
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<issn pub-type="epub">1932-6203</issn>
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<publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, CA USA</publisher-loc>
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<article-id pub-id-type="pmid">26599971</article-id>
<article-id pub-id-type="pmc">4658036</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0143388</article-id>
<article-id pub-id-type="publisher-id">PONE-D-15-31636</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>
<italic>Helicobacter pylori</italic>
Infection Is Associated with Higher CD4 T Cell Counts and Lower HIV-1 Viral Loads in ART-Naïve HIV-Positive Patients in Ghana</article-title>
<alt-title alt-title-type="running-head">HIV and
<italic>H</italic>
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<italic>pylori</italic>
Co-Infection in Ghana</alt-title>
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<contrib-group>
<contrib contrib-type="author">
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<surname>Sarfo</surname>
<given-names>Fred Stephen</given-names>
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<xref ref-type="aff" rid="aff001">
<sup>1</sup>
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<sup>2</sup>
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<surname>Eberhardt</surname>
<given-names>Kirsten Alexandra</given-names>
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<xref ref-type="aff" rid="aff003">
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<xref ref-type="aff" rid="aff002">
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<surname>Kuffour</surname>
<given-names>Edmund Osei</given-names>
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<xref ref-type="aff" rid="aff005">
<sup>5</sup>
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<given-names>Anna Maria</given-names>
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<xref ref-type="aff" rid="aff005">
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<xref ref-type="aff" rid="aff004">
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<surname>Oteng-Seifah</surname>
<given-names>Emelia Efua</given-names>
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<xref ref-type="aff" rid="aff006">
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<surname>Bedu-Addo</surname>
<given-names>George</given-names>
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<xref ref-type="aff" rid="aff001">
<sup>1</sup>
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<xref ref-type="aff" rid="aff002">
<sup>2</sup>
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<surname>Phillips</surname>
<given-names>Richard Odame</given-names>
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<xref ref-type="aff" rid="aff001">
<sup>1</sup>
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<xref ref-type="aff" rid="aff002">
<sup>2</sup>
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<xref ref-type="aff" rid="aff001">
<sup>1</sup>
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<xref ref-type="aff" rid="aff002">
<sup>2</sup>
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<xref ref-type="aff" rid="aff003">
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<sup>4</sup>
</xref>
<xref rid="cor001" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="aff001">
<label>1</label>
<addr-line>Kwame Nkrumah University of Science and Technology, Kumasi, Ghana</addr-line>
</aff>
<aff id="aff002">
<label>2</label>
<addr-line>Komfo Anokye Teaching Hospital, Kumasi, Ghana</addr-line>
</aff>
<aff id="aff003">
<label>3</label>
<addr-line>Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany</addr-line>
</aff>
<aff id="aff004">
<label>4</label>
<addr-line>Clinic of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, Germany</addr-line>
</aff>
<aff id="aff005">
<label>5</label>
<addr-line>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany</addr-line>
</aff>
<aff id="aff006">
<label>6</label>
<addr-line>Kumasi Centre for Collaborative Research, Kumasi, Ghana</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Apetrei</surname>
<given-names>Cristian</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>University of Pittsburgh Center for Vaccine Research, UNITED STATES</addr-line>
</aff>
<author-notes>
<fn fn-type="conflict" id="coi001">
<p>
<bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con" id="contrib001">
<p>Conceived and designed the experiments: FSS KAE AD EOK MS MS JFD AME DH EEOS GBA ROP BN GB TF. Performed the experiments: FSS KAE AD EOK MS MS JFD AME DH EEOS TF. Analyzed the data: FSS KAE AD EOK TF. Contributed reagents/materials/analysis tools: AD JFD AME DH EEOS GBA ROP BN GB TF. Wrote the paper: FSS KAE AD EOK MS MS JFD AME DH EEOS GBA ROP BN GB TF.</p>
</fn>
<corresp id="cor001">* E-mail:
<email>Torsten.Feldt@med.uni-duesseldorf.de</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>24</day>
<month>11</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="collection">
<year>2015</year>
</pub-date>
<volume>10</volume>
<issue>11</issue>
<elocation-id>e0143388</elocation-id>
<history>
<date date-type="received">
<day>19</day>
<month>7</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>4</day>
<month>11</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-year>2015</copyright-year>
<copyright-holder>Sarfo et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:type="simple" xlink:href="pone.0143388.pdf"></self-uri>
<abstract>
<sec id="sec001">
<title>Background</title>
<p>Worldwide, there is a high co-endemicity of HIV and
<italic>H</italic>
.
<italic>pylori</italic>
infection and there is growing evidence that
<italic>H</italic>
.
<italic>pylori</italic>
co-infection is associated with parameters of HIV disease progression. The objective of this study was to investigate the prevalence of
<italic>H</italic>
.
<italic>pylori</italic>
infection, and the association with clinical, immunological and virological parameters in a large cohort of HIV-infected individuals and uninfected controls in a West African country.</p>
</sec>
<sec id="sec002">
<title>Methods</title>
<p>HIV-patients (n = 1,095) and HIV-negative individuals (n = 107) were recruited at a university hospital in Ghana.
<italic>H</italic>
.
<italic>pylori</italic>
status was determined using stool antigen testing. HIV-related, clinical and socio-demographic parameters were recorded and analyzed according to
<italic>H</italic>
.
<italic>pylori</italic>
status.</p>
</sec>
<sec id="sec003">
<title>Results</title>
<p>The prevalence of
<italic>H</italic>
.
<italic>pylori</italic>
infection was significantly lower in HIV-positive compared to HIV-negative individuals (51.5 vs. 88%, p<0.0001). In HIV patients,
<italic>H</italic>
.
<italic>pylori</italic>
prevalence decreased in parallel with CD4+ T cell counts. In ART-naïve HIV-infected individuals, but not in those taking ART,
<italic>H</italic>
.
<italic>pylori</italic>
infection was associated with higher CD4 cell counts (312 vs. 189 cells/μL, p<0.0001) and lower HIV-1 viral loads (4.92 vs. 5.21 log10 copies/mL, p = 0.006). The findings could not be explained by socio-demographic confounders or reported use of antibiotics. Having no access to tap water and higher CD4+ T cell counts were identified as risk factors for
<italic>H</italic>
.
<italic>pylori</italic>
infection.</p>
</sec>
<sec id="sec004">
<title>Conclusions</title>
<p>
<italic>H</italic>
.
<italic>pylori</italic>
prevalence was inversely correlated with the degree of immunosuppression. In ART-naïve individuals,
<italic>H</italic>
.
<italic>pylori</italic>
infection is associated with favorable immunological and virological parameters. The underlying mechanisms for this association are unclear and warrant investigation.</p>
</sec>
</abstract>
<funding-group>
<funding-statement>This work was supported by the German Federal Ministry of Education and Research [grant number 01KA1102 ]. The funders had no role in the design of the study and decision to publish these findings.</funding-statement>
</funding-group>
<counts>
<fig-count count="1"></fig-count>
<table-count count="4"></table-count>
<page-count count="12"></page-count>
</counts>
<custom-meta-group>
<custom-meta id="data-availability">
<meta-name>Data Availability</meta-name>
<meta-value>Data contain sensitive participant information and are available upon request from the corresponding author.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes>
<title>Data Availability</title>
<p>Data contain sensitive participant information and are available upon request from the corresponding author.</p>
</notes>
</front>
<body>
<sec sec-type="intro" id="sec005">
<title>Introduction</title>
<p>Recently, the interplay between the Human immunodeficiency virus (HIV) and
<italic>Helicobacter pylori</italic>
(
<italic>H</italic>
.
<italic>pylori</italic>
) infection has attracted attention. A number of studies have reported lower
<italic>H</italic>
.
<italic>pylori</italic>
prevalence rates in HIV-infected compared to HIV-negative individuals [
<xref rid="pone.0143388.ref001" ref-type="bibr">1</xref>
,
<xref rid="pone.0143388.ref002" ref-type="bibr">2</xref>
]. This association is unexpected, since usually chronic infections are more commonly found in patients with advanced HIV disease. Furthermore,
<italic>H</italic>
.
<italic>pylori</italic>
infection is considered a disease of poverty, and poor socioeconomic status has been associated with rather disadvantageous outcomes of HIV infection [
<xref rid="pone.0143388.ref003" ref-type="bibr">3</xref>
]. The underlying mechanisms for this observed association are unclear. Most existing studies have important limitations such as small sample sizes thus preventing subgroup analyses and robust adjustment for confounders. In particular, information on socio-economic variables, as putative confounders for
<italic>H</italic>
.
<italic>pylori</italic>
status is sorely lacking. As a consequence, interpretation and comparison of results are difficult and data published to date is partly inconsistent [
<xref rid="pone.0143388.ref002" ref-type="bibr">2</xref>
].</p>
<p>Considering the significant epidemiological and pathophysiological overlap of HIV and
<italic>H</italic>
.
<italic>pylori</italic>
infection, the investigation of possible interplay is of interest. Over the past few years it has become clear, that the gastrointestinal tract (GIT) plays an important role in the pathophysiology of HIV/AIDS. Chronic immune activation, associated with intestinal barrier dysfunction, has been identified as central pathomechanism in HIV disease [
<xref rid="pone.0143388.ref004" ref-type="bibr">4</xref>
].
<italic>H</italic>
.
<italic>pylori</italic>
colonize the gastric and duodenal mucosae and induce a specific local and also systemic immune response, involving, among others, CD4+ T cells, dendritic cells, regulatory T cells (Treg) and Th17 cells, with all of these also playing a role in HIV pathogenesis [
<xref rid="pone.0143388.ref005" ref-type="bibr">5</xref>
<xref rid="pone.0143388.ref008" ref-type="bibr">8</xref>
].</p>
<p>The association of HIV and
<italic>H</italic>
.
<italic>pylori</italic>
co-infection has not been systematically studied in sub-Saharan Africa, where more than two thirds of HIV-infected individuals live, and where, at the same time, the vast majority of the population gets infected with
<italic>H</italic>
.
<italic>pylori</italic>
during childhood [
<xref rid="pone.0143388.ref009" ref-type="bibr">9</xref>
<xref rid="pone.0143388.ref011" ref-type="bibr">11</xref>
]. The objective of this study was to investigate the prevalence of
<italic>H</italic>
.
<italic>pylori</italic>
infection, and its association with clinical, immunological and virological parameters in a large cohort of HIV-infected individuals and uninfected controls in a West African country.</p>
</sec>
<sec sec-type="materials|methods" id="sec006">
<title>Materials & Methods</title>
<sec id="sec007">
<title>Study setting and recruitment</title>
<p>This cross-sectional study was conducted at the Komfo Anokye Teaching Hospital, a tertiary referral hospital in the Ashanti Region of Ghana. Between November 2011 and November 2012, consecutive adult HIV-infected patients presenting to the HIV outpatient clinic, and HIV-negative blood donors presenting to the blood bank of the hospital, were offered participation in the study. All participants gave a written informed consent prior to enrolment. The study was conducted in conformity with the Helsinki declaration, and was approved by the appropriate ethics committees of the Kwame Nkrumah University of Science and Technology (Ghana) and of the medical association in Hamburg (Germany).</p>
</sec>
<sec id="sec008">
<title>Data collection and measures</title>
<p>Demographic, socioeconomic, and clinical data, as well as a detailed medical history were recorded using standardized questionnaires, which were completed by trained study personnel. In particular, time since diagnosis of HIV infection, duration and kind of antiretroviral therapy (ART), co-medications, and clinical parameters were documented. Routine laboratory parameters were extracted from patient’s folders. EDTA blood samples were obtained for the analysis of CD4/CD8 T cell counts, using a FACSCalibur® flow cytometer (Becton Dickinson, USA). HIV-1 and 2 antibody testing was done using the First Response® HIV-1/2 test (Premier Medical Corporation Limited, India) and the Genscreen® ULTRA HIV Ag-Ab Assay (Bio-Rad, France). EDTA plasma and native stool samples were freshly frozen at -80°C and transported to Germany on dry ice. Stool was tested for
<italic>H</italic>
.
<italic>pylori</italic>
using the RidaScreen® FemtoLab
<italic>H</italic>
.
<italic>pylori</italic>
stool antigen test (R-Biopharm AG, Germany). The sensitivity and specificity of this test has been described to be 98% and 96.7% in pediatric patients and 93% and 90% in adult patients [
<xref rid="pone.0143388.ref012" ref-type="bibr">12</xref>
,
<xref rid="pone.0143388.ref013" ref-type="bibr">13</xref>
]. HIV-1 viral load was measured using the RealTime HIV-1 PCR system (Abbott Diagnostics, Wiesbaden, Germany) according to the manufacturer’s instructions. The same tests, except HIV-1 viral load analysis, were conducted for cases and controls.</p>
</sec>
<sec id="sec009">
<title>Statistical analysis</title>
<p>Parametric variables were compared using the Student’s t-test, non-parametric variables were compared using the Mann-Whitney U-test. Categorical data were analyzed using Chi-squared or Fisher’s exact test. A multivariable logistic regression model was used to analyze the association between
<italic>H</italic>
.
<italic>pylori</italic>
infection and other demographic, clinical and laboratory parameters, using only parameters with a significance level of ≤0.05 in bivariate analysis and a correlation coefficient of ≤0.10 in the multivariate regression model. Missing data were excluded from analysis. Statistical analyses were conducted with SPSS version 19 software (IBM, Germany).</p>
</sec>
</sec>
<sec sec-type="results" id="sec010">
<title>Results</title>
<sec id="sec011">
<title>Cohort characteristics</title>
<p>We recruited 1,095 HIV-positive individuals and 107 HIV-negative blood donors. Stool samples for
<italic>H</italic>
.
<italic>pylori</italic>
testing were available for 952 HIV-positive (86.9%) and 100 HIV-negative individuals (93.5%). HIV-positive, compared to HIV-negative individuals, were more often female, significantly older, had a lower BMI, lower socioeconomic status, lower CD4 and higher CD8 T cell counts (
<xref rid="pone.0143388.t001" ref-type="table">Table 1</xref>
). The majority of HIV-infected participants were female (75.6%), and the mean age was 40 years. Approximately half of HIV-positive individuals (n = 500, 52.5%) were ART-naïve at the time of recruitment, 452 (47.5%) patients were receiving ART for a median duration of 45 months (IQR 19–69). Participants receiving ART, compared to ART-naïve participants, were more likely to be female, had a higher BMI, higher total absolute lymphocyte and CD4 T cell counts compared to ART-naïve HIV-positive participants (
<xref rid="pone.0143388.s001" ref-type="supplementary-material">S1 Table</xref>
).</p>
<table-wrap id="pone.0143388.t001" orientation="portrait" position="float">
<object-id pub-id-type="doi">10.1371/journal.pone.0143388.t001</object-id>
<label>Table 1</label>
<caption>
<title>Comparison of demographic and laboratory characteristics of HIV-positive and HIV-negative participants.</title>
</caption>
<alternatives>
<graphic id="pone.0143388.t001g" xlink:href="pone.0143388.t001"></graphic>
<table frame="hsides" rules="groups">
<colgroup span="1">
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
</colgroup>
<thead>
<tr>
<th align="left" rowspan="1" colspan="1">Variable</th>
<th align="center" rowspan="1" colspan="1">HIV-positive</th>
<th align="center" rowspan="1" colspan="1">HIV-negative</th>
<th align="center" rowspan="1" colspan="1">p-value</th>
</tr>
<tr>
<th align="left" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">N = 952</th>
<th align="center" rowspan="1" colspan="1">N = 100</th>
<th align="center" rowspan="1" colspan="1"></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">Female gender, n (%)</td>
<td align="center" rowspan="1" colspan="1">720 (75.6)</td>
<td align="center" rowspan="1" colspan="1">66 (66.0)</td>
<td align="center" rowspan="1" colspan="1">0.04</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Age (years), mean ± SD</td>
<td align="center" rowspan="1" colspan="1">40 ± 9.5</td>
<td align="center" rowspan="1" colspan="1">33 ± 12.3</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Religion, n (%)
<xref rid="t001fn002" ref-type="table-fn">
<sup>#</sup>
</xref>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.12</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Christian</td>
<td align="center" rowspan="1" colspan="1">814 (85.5)</td>
<td align="center" rowspan="1" colspan="1">86 (92.5)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Moslem</td>
<td align="center" rowspan="1" colspan="1">120 (12.6)</td>
<td align="center" rowspan="1" colspan="1">6 (6.5)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Traditional African religion</td>
<td align="center" rowspan="1" colspan="1">2 (0.2)</td>
<td align="center" rowspan="1" colspan="1">0 (0.0)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Other</td>
<td align="center" rowspan="1" colspan="1">16 (1.7)</td>
<td align="center" rowspan="1" colspan="1">1(1.0)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Educational level, n (%)
<xref rid="t001fn002" ref-type="table-fn">
<sup>#</sup>
</xref>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Primary education</td>
<td align="center" rowspan="1" colspan="1">156 (16.4)</td>
<td align="center" rowspan="1" colspan="1">9 (9.7)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Junior Secondary School</td>
<td align="center" rowspan="1" colspan="1">426 (44.7)</td>
<td align="center" rowspan="1" colspan="1">7 (7.5)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Senior Secondary School</td>
<td align="center" rowspan="1" colspan="1">133 (14.0)</td>
<td align="center" rowspan="1" colspan="1">56 (60.2)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Tertiary education</td>
<td align="center" rowspan="1" colspan="1">51 (5.4)</td>
<td align="center" rowspan="1" colspan="1">14 (15.1)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">No formal education</td>
<td align="center" rowspan="1" colspan="1">186 (19.5)</td>
<td align="center" rowspan="1" colspan="1">7 (7.5)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Occupation, n (%)
<xref rid="t001fn002" ref-type="table-fn">
<sup>#</sup>
</xref>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">House wife</td>
<td align="center" rowspan="1" colspan="1">13 (1.4)</td>
<td align="center" rowspan="1" colspan="1">1(1.1)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Farmer</td>
<td align="center" rowspan="1" colspan="1">78 (8.2)</td>
<td align="center" rowspan="1" colspan="1">2 (2.2)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Trader</td>
<td align="center" rowspan="1" colspan="1">505 (53.0)</td>
<td align="center" rowspan="1" colspan="1">33 (35.5)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Salary worker</td>
<td align="center" rowspan="1" colspan="1">60 (6.3)</td>
<td align="center" rowspan="1" colspan="1">27 (29.0)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Others</td>
<td align="center" rowspan="1" colspan="1">114 (12.0)</td>
<td align="center" rowspan="1" colspan="1">4 (4.3)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Currently unemployed</td>
<td align="center" rowspan="1" colspan="1">182 (19.1)</td>
<td align="center" rowspan="1" colspan="1">24 (25.8)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Access to tap water, n (%)
<xref rid="t001fn003" ref-type="table-fn">*</xref>
</td>
<td align="center" rowspan="1" colspan="1">501 (52.6)</td>
<td align="center" rowspan="1" colspan="1">61 (63.5)</td>
<td align="center" rowspan="1" colspan="1">0.04</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<italic>H</italic>
.
<italic>pylori</italic>
test result, n (%)</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Positive</td>
<td align="center" rowspan="1" colspan="1">490 (51.5)</td>
<td align="center" rowspan="1" colspan="1">88 (88.0)</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Negative</td>
<td align="center" rowspan="1" colspan="1">452 (47.5)</td>
<td align="center" rowspan="1" colspan="1">12 (12.0)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Indeterminate</td>
<td align="center" rowspan="1" colspan="1">10 (1.0)</td>
<td align="center" rowspan="1" colspan="1">0 (0.0)</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">BMI (kg/m
<sup>2</sup>
), mean ± SD</td>
<td align="center" rowspan="1" colspan="1">23.1 ± 4.6</td>
<td align="center" rowspan="1" colspan="1">24.7 ± 5.0</td>
<td align="center" rowspan="1" colspan="1">0.002</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">T-cell populations, median (IQR)</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Total T-cell count/μL</td>
<td align="center" rowspan="1" colspan="1">1,381 (984–1,968)</td>
<td align="center" rowspan="1" colspan="1">1,460 (1,171–1,895)</td>
<td align="center" rowspan="1" colspan="1">0.13</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">CD4 T-cell count/μL</td>
<td align="center" rowspan="1" colspan="1">380 (173–596)</td>
<td align="center" rowspan="1" colspan="1">958 (786–1,161)</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">CD8 T-cell count/μL</td>
<td align="center" rowspan="1" colspan="1">914 (620–1,341)</td>
<td align="center" rowspan="1" colspan="1">439 (312–673)</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
</tr>
</tbody>
</table>
</alternatives>
<table-wrap-foot>
<fn id="t001fn001">
<p>BMI, Body mass index</p>
</fn>
<fn id="t001fn002">
<p>
<sup>#</sup>
missing data for 7 participants of the HIV negative group.</p>
</fn>
<fn id="t001fn003">
<p>* Missing data for 4 participants of the HIV-negative group.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec012">
<title>
<italic>H</italic>
.
<italic>pylori</italic>
infection</title>
<p>The prevalence of
<italic>H</italic>
.
<italic>pylori</italic>
infection among HIV-negative individuals was significantly higher compared to HIV-positive individuals (88.0% vs. 51.5%, p<0.0001). In HIV-positive individuals,
<italic>H</italic>
.
<italic>pylori</italic>
prevalence declined in parallel with CD4+ T cell counts, from 64.8% in patients with more than 800 CD4 T cells/μL, to 41.4% in patients with less than 200 CD4 T cells/μL. The same trend was observed in HIV-negative individuals, without reaching statistical significance (
<xref rid="pone.0143388.g001" ref-type="fig">Fig 1</xref>
).</p>
<fig id="pone.0143388.g001" orientation="portrait" position="float">
<object-id pub-id-type="doi">10.1371/journal.pone.0143388.g001</object-id>
<label>Fig 1</label>
<caption>
<title>Comparison of
<italic>H</italic>
.
<italic>pylori</italic>
prevalence according to CD4 T cell count/μL for HIV-positive participants (p = 0.001, Chi-square test) and for HIV-negative individuals (p = 0.397, Chi-square test); N = Group sizes for CD4 T cell categories including
<italic>H</italic>
.
<italic>pylori</italic>
positive and negative participants.</title>
</caption>
<graphic xlink:href="pone.0143388.g001"></graphic>
</fig>
<p>The characteristics of HIV-infected individuals according to
<italic>H</italic>
.
<italic>pylori</italic>
status are shown in
<xref rid="pone.0143388.t002" ref-type="table">Table 2</xref>
.
<italic>H</italic>
.
<italic>pylori</italic>
co-infected HIV-positive patients were significantly less likely to have access to tap water (48.8 vs. 58.0%, p = 0.005) and less likely to have attained a tertiary level education (3.7 vs. 7.3%, p = 0.01). There were no significant differences in other demographic variables assessed, or in WHO clinical HIV disease stages (
<xref rid="pone.0143388.t003" ref-type="table">Table 3</xref>
).</p>
<table-wrap id="pone.0143388.t002" orientation="portrait" position="float">
<object-id pub-id-type="doi">10.1371/journal.pone.0143388.t002</object-id>
<label>Table 2</label>
<caption>
<title>Comparison of socio-demographic parameters of HIV-infected participants according to
<italic>H</italic>
.
<italic>pylori</italic>
status.</title>
</caption>
<alternatives>
<graphic id="pone.0143388.t002g" xlink:href="pone.0143388.t002"></graphic>
<table frame="hsides" rules="groups">
<colgroup span="1">
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
</colgroup>
<thead>
<tr>
<th align="left" rowspan="1" colspan="1">Variable</th>
<th align="left" rowspan="1" colspan="1">
<italic>H</italic>
.
<italic>pylori</italic>
positive</th>
<th align="left" rowspan="1" colspan="1">
<italic>H</italic>
.
<italic>pylori</italic>
negative</th>
<th align="left" rowspan="1" colspan="1">p-value</th>
</tr>
<tr>
<th align="left" rowspan="1" colspan="1"></th>
<th align="left" rowspan="1" colspan="1">N = 490</th>
<th align="left" rowspan="1" colspan="1">N = 452</th>
<th align="left" rowspan="1" colspan="1"></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">Female gender, n (%)</td>
<td align="left" rowspan="1" colspan="1">372 (75.9)</td>
<td align="left" rowspan="1" colspan="1">339 (75.0)</td>
<td align="left" rowspan="1" colspan="1">0.74</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Age (years), mean ± SD</td>
<td align="left" rowspan="1" colspan="1">40 ± 9.4</td>
<td align="left" rowspan="1" colspan="1">40 ± 9.6</td>
<td align="left" rowspan="1" colspan="1">0.97</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Religion, n (%)
<sup>#</sup>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Christian</td>
<td align="left" rowspan="1" colspan="1">410 (83.7)</td>
<td align="left" rowspan="1" colspan="1">396 (87.6)</td>
<td align="left" rowspan="1" colspan="1">0.12</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Moslem</td>
<td align="left" rowspan="1" colspan="1">71 (14.5)</td>
<td align="left" rowspan="1" colspan="1">47 (10.4)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Traditional African religion</td>
<td align="left" rowspan="1" colspan="1">2 (0.4)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Other</td>
<td align="left" rowspan="1" colspan="1">7 (1.4)</td>
<td align="left" rowspan="1" colspan="1">9 (2.0)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Educational level, n (%)
<sup>#</sup>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">0.08</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">No formal education</td>
<td align="left" rowspan="1" colspan="1">91 (18.6)</td>
<td align="left" rowspan="1" colspan="1">91 (20.1)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Primary education</td>
<td align="left" rowspan="1" colspan="1">84 (17.1)</td>
<td align="left" rowspan="1" colspan="1">72 (15.9)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Secondary education</td>
<td align="left" rowspan="1" colspan="1">297 (60.6)</td>
<td align="left" rowspan="1" colspan="1">256 (56.6)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Tertiary education</td>
<td align="left" rowspan="1" colspan="1">18 (3.7)</td>
<td align="left" rowspan="1" colspan="1">33 (7.3)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Occupation, n (%)
<sup>##</sup>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">0.75</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">House wife</td>
<td align="left" rowspan="1" colspan="1">6 (1.2)</td>
<td align="left" rowspan="1" colspan="1">7 (1.5)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Farmer</td>
<td align="left" rowspan="1" colspan="1">42 (8.6)</td>
<td align="left" rowspan="1" colspan="1">36 (8.0)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Trader</td>
<td align="left" rowspan="1" colspan="1">257 (52.4)</td>
<td align="left" rowspan="1" colspan="1">242 (53.5)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Salary worker</td>
<td align="left" rowspan="1" colspan="1">27 (5.5)</td>
<td align="left" rowspan="1" colspan="1">33 (7.3)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Others</td>
<td align="left" rowspan="1" colspan="1">64 (13.1)</td>
<td align="left" rowspan="1" colspan="1">48 (10.6)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Currently unemployed</td>
<td align="left" rowspan="1" colspan="1">94 (19.2)</td>
<td align="left" rowspan="1" colspan="1">86 (19.0)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Access to tap water, n (%)</td>
<td align="left" rowspan="1" colspan="1">239 (48.8)</td>
<td align="left" rowspan="1" colspan="1">262 (58.0)</td>
<td align="left" rowspan="1" colspan="1">0.005</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Electricity in the household, n (%)</td>
<td align="left" rowspan="1" colspan="1">452 (92.2)</td>
<td align="left" rowspan="1" colspan="1">420 (92.9)</td>
<td align="left" rowspan="1" colspan="1">0.39</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Television in household, n (%)</td>
<td align="left" rowspan="1" colspan="1">398 (81.2)</td>
<td align="left" rowspan="1" colspan="1">366 (81.0)</td>
<td align="left" rowspan="1" colspan="1">0.92</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Owning a fridge, n (%)</td>
<td align="left" rowspan="1" colspan="1">336 (68.6)</td>
<td align="left" rowspan="1" colspan="1">322 (71.2)</td>
<td align="left" rowspan="1" colspan="1">0.89</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Owning a car, n (%)</td>
<td align="left" rowspan="1" colspan="1">35 (7.1)</td>
<td align="left" rowspan="1" colspan="1">51 (11.3)</td>
<td align="left" rowspan="1" colspan="1">0.03</td>
</tr>
</tbody>
</table>
</alternatives>
<table-wrap-foot>
<fn id="t002fn001">
<p>Analysis excludes 10 patients with indeterminate H. pylori result.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="pone.0143388.t003" orientation="portrait" position="float">
<object-id pub-id-type="doi">10.1371/journal.pone.0143388.t003</object-id>
<label>Table 3</label>
<caption>
<title>Comparison of clinical and laboratory parameters in HIV-positive and HIV-negative individuals according to H. pylori status.</title>
</caption>
<alternatives>
<graphic id="pone.0143388.t003g" xlink:href="pone.0143388.t003"></graphic>
<table frame="hsides" rules="groups">
<colgroup span="1">
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
</colgroup>
<thead>
<tr>
<th rowspan="2" align="left" colspan="1">Variable</th>
<th colspan="3" align="center" rowspan="1">ART-naïve group, n = 494</th>
<th colspan="3" align="center" rowspan="1">ART group, n = 448</th>
<th colspan="3" align="center" rowspan="1">HIV negative group, n = 100</th>
</tr>
<tr>
<th align="center" rowspan="1" colspan="1">
<italic>H</italic>
.
<italic>pylori</italic>
pos.</th>
<th align="center" rowspan="1" colspan="1">
<italic>H</italic>
.
<italic>pylori</italic>
neg.</th>
<th align="center" rowspan="1" colspan="1">p-value</th>
<th align="center" rowspan="1" colspan="1">
<italic>H</italic>
.
<italic>pylori</italic>
pos.</th>
<th align="center" rowspan="1" colspan="1">
<italic>H</italic>
.
<italic>pylori</italic>
neg.</th>
<th align="center" rowspan="1" colspan="1">p-value</th>
<th align="center" rowspan="1" colspan="1">
<italic>H</italic>
.
<italic>pylori</italic>
pos.</th>
<th align="center" rowspan="1" colspan="1">
<italic>H</italic>
.
<italic>pylori</italic>
neg.</th>
<th align="center" rowspan="1" colspan="1">p-value</th>
</tr>
<tr>
<th align="left" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">N = 239 (48.4%)</th>
<th align="center" rowspan="1" colspan="1">N = 255 (51.6%)</th>
<th align="center" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">N = 251 (56.0%)</th>
<th align="center" rowspan="1" colspan="1">N = 197 (44.0%)</th>
<th align="center" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">N = 88 (88.0%)</th>
<th align="center" rowspan="1" colspan="1">N = 12 (12.0%)</th>
<th align="center" rowspan="1" colspan="1"></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>Time since HIV diagnosis</bold>
(months), median (IQR)</td>
<td align="left" rowspan="1" colspan="1">0.5 (0.5–3.5)</td>
<td align="left" rowspan="1" colspan="1">0.5 (0.5–1.0)</td>
<td align="left" rowspan="1" colspan="1">0.006</td>
<td align="left" rowspan="1" colspan="1">53 (24–82)</td>
<td align="left" rowspan="1" colspan="1">53 (25–74)</td>
<td align="left" rowspan="1" colspan="1">0.42</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>Time on ART</bold>
(months) median (IQR)</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">45 (18–70)</td>
<td align="left" rowspan="1" colspan="1">47 (22–68)</td>
<td align="left" rowspan="1" colspan="1">0.98</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>WHO stage</bold>
<xref rid="t003fn002" ref-type="table-fn">
<sup>#</sup>
</xref>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">0.22</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">0.15</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">1</td>
<td align="left" rowspan="1" colspan="1">109 (45.6)</td>
<td align="left" rowspan="1" colspan="1">118 (46.3)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">139 (55.4)</td>
<td align="left" rowspan="1" colspan="1">117 (59.4)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">2</td>
<td align="left" rowspan="1" colspan="1">23 (9.6)</td>
<td align="left" rowspan="1" colspan="1">31 (12.2)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">34 (13.5)</td>
<td align="left" rowspan="1" colspan="1">13 (6.6)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">3</td>
<td align="left" rowspan="1" colspan="1">28 (11.7)</td>
<td align="left" rowspan="1" colspan="1">38 (14.9)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">35 (13.9)</td>
<td align="left" rowspan="1" colspan="1">28 (14.2)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">4</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">2 (0.8)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">2 (0.8)</td>
<td align="left" rowspan="1" colspan="1">4 (2.0)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">No data</td>
<td align="left" rowspan="1" colspan="1">79 (33.1)</td>
<td align="left" rowspan="1" colspan="1">66 (25.9)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">41 (16.3)</td>
<td align="left" rowspan="1" colspan="1">35 (17.8)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>Exposure to TB treatment</bold>
, n (%)</td>
<td align="left" rowspan="1" colspan="1">21 (8.8)</td>
<td align="left" rowspan="1" colspan="1">41 (16.1)</td>
<td align="left" rowspan="1" colspan="1">0.01</td>
<td align="left" rowspan="1" colspan="1">24 (9.6)</td>
<td align="left" rowspan="1" colspan="1">17 (8.6)</td>
<td align="left" rowspan="1" colspan="1">0.87</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Currently on TB treatment, n (%)</td>
<td align="left" rowspan="1" colspan="1">8 (3.3)</td>
<td align="left" rowspan="1" colspan="1">25 (9.8)</td>
<td align="left" rowspan="1" colspan="1">0.004</td>
<td align="left" rowspan="1" colspan="1">1 (0.4)</td>
<td align="left" rowspan="1" colspan="1">2 (1.0)</td>
<td align="left" rowspan="1" colspan="1">0.58</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Previous TB treatment, n (%)</td>
<td align="left" rowspan="1" colspan="1">13 (5.4)</td>
<td align="left" rowspan="1" colspan="1">16 (6.3)</td>
<td align="left" rowspan="1" colspan="1">0.69</td>
<td align="left" rowspan="1" colspan="1">23 (9.2)</td>
<td align="left" rowspan="1" colspan="1">15 (7.6)</td>
<td align="left" rowspan="1" colspan="1">0.56</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>Antibiotic use</bold>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Antibiotic use past six months, n (%)</td>
<td align="left" rowspan="1" colspan="1">3 (1.3)</td>
<td align="left" rowspan="1" colspan="1">2 (0.8)</td>
<td align="left" rowspan="1" colspan="1">0.68</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">1 (O.5)</td>
<td align="left" rowspan="1" colspan="1">0.58</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Current use of co-trimoxazole, n (%)</td>
<td align="left" rowspan="1" colspan="1">62 (25.9)</td>
<td align="left" rowspan="1" colspan="1">80 (31.4)</td>
<td align="left" rowspan="1" colspan="1">0.18</td>
<td align="left" rowspan="1" colspan="1">49 (19.5)</td>
<td align="left" rowspan="1" colspan="1">48 (24.4)</td>
<td align="left" rowspan="1" colspan="1">0.25</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>Self-reported symptoms</bold>
<xref rid="t003fn004" ref-type="table-fn">*</xref>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Epigastric discomfort</td>
<td align="left" rowspan="1" colspan="1">24 (10.0)</td>
<td align="left" rowspan="1" colspan="1">24 (9.4)</td>
<td align="left" rowspan="1" colspan="1">0.81</td>
<td align="left" rowspan="1" colspan="1">5 (2.0)</td>
<td align="left" rowspan="1" colspan="1">8 (4.1)</td>
<td align="left" rowspan="1" colspan="1">0.20</td>
<td align="left" rowspan="1" colspan="1">18 (21.4)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">0.08</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Anorexia</td>
<td align="left" rowspan="1" colspan="1">6 (2.5)</td>
<td align="left" rowspan="1" colspan="1">12 (4.7)</td>
<td align="left" rowspan="1" colspan="1">0.19</td>
<td align="left" rowspan="1" colspan="1">2 (0.8)</td>
<td align="left" rowspan="1" colspan="1">5 (2.5)</td>
<td align="left" rowspan="1" colspan="1">0.14</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Nausea and vomiting</td>
<td align="left" rowspan="1" colspan="1">9 (3.8)</td>
<td align="left" rowspan="1" colspan="1">16 (6.3)</td>
<td align="left" rowspan="1" colspan="1">0.11</td>
<td align="left" rowspan="1" colspan="1">2 (0.8)</td>
<td align="left" rowspan="1" colspan="1">6 (3.0)</td>
<td align="left" rowspan="1" colspan="1">0.07</td>
<td align="left" rowspan="1" colspan="1">2 (2.4)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">0.68</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Diarrhea</td>
<td align="left" rowspan="1" colspan="1">23 (9.6)</td>
<td align="left" rowspan="1" colspan="1">23 (9.0)</td>
<td align="left" rowspan="1" colspan="1">0.82</td>
<td align="left" rowspan="1" colspan="1">5 (2.0)</td>
<td align="left" rowspan="1" colspan="1">1 (0.5)</td>
<td align="left" rowspan="1" colspan="1">0.17</td>
<td align="left" rowspan="1" colspan="1">12 (14.3)</td>
<td align="left" rowspan="1" colspan="1">2 (16.7)</td>
<td align="left" rowspan="1" colspan="1">0.83</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Weight loss</td>
<td align="left" rowspan="1" colspan="1">78 (32.6)</td>
<td align="left" rowspan="1" colspan="1">102 (40.0)</td>
<td align="left" rowspan="1" colspan="1">0.09</td>
<td align="left" rowspan="1" colspan="1">15 (6.0)</td>
<td align="left" rowspan="1" colspan="1">16 (8.1)</td>
<td align="left" rowspan="1" colspan="1">0.37</td>
<td align="left" rowspan="1" colspan="1">4 (4.5)</td>
<td align="left" rowspan="1" colspan="1">0 (0.0)</td>
<td align="left" rowspan="1" colspan="1">0.83</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>Body Mass Index</bold>
(kg/m
<sup>2</sup>
), mean ±SD</td>
<td align="left" rowspan="1" colspan="1">22.4 ± 4.1</td>
<td align="left" rowspan="1" colspan="1">21.9 ± 4.2</td>
<td align="left" rowspan="1" colspan="1">0.19</td>
<td align="left" rowspan="1" colspan="1">24.3 ± 4.5</td>
<td align="left" rowspan="1" colspan="1">23.8 ± 4.6</td>
<td align="left" rowspan="1" colspan="1">0.21</td>
<td align="left" rowspan="1" colspan="1">24.7 ± 5.0</td>
<td align="left" rowspan="1" colspan="1">24.6 ± 5.6</td>
<td align="left" rowspan="1" colspan="1">0.96</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>HIV-1 VL (</bold>
log 10 c/mL), median (IQR)
<xref rid="t003fn003" ref-type="table-fn">
<sup>§</sup>
</xref>
</td>
<td align="left" rowspan="1" colspan="1">4.92 (4.09–5.51)</td>
<td align="left" rowspan="1" colspan="1">5.21 (4.59–5.63)</td>
<td align="left" rowspan="1" colspan="1">0.006</td>
<td align="left" rowspan="1" colspan="1">3.67 (3.10–4.57)</td>
<td align="left" rowspan="1" colspan="1">3.09 (2.31–4.71)</td>
<td align="left" rowspan="1" colspan="1">0.54</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>T-cell populations</bold>
, median (IQR)</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">Total T-cell count/μL</td>
<td align="left" rowspan="1" colspan="1">1227 (867–1929)</td>
<td align="left" rowspan="1" colspan="1">1253(794–1921)</td>
<td align="left" rowspan="1" colspan="1">0.94</td>
<td align="left" rowspan="1" colspan="1">1452 (1108–1934)</td>
<td align="left" rowspan="1" colspan="1">1584 (1151–2083)</td>
<td align="left" rowspan="1" colspan="1">0.05</td>
<td align="left" rowspan="1" colspan="1">1439 (1166–1910)</td>
<td align="left" rowspan="1" colspan="1">1520 (1318–1717)</td>
<td align="left" rowspan="1" colspan="1">0.79</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">CD4 T-cell count/μL</td>
<td align="left" rowspan="1" colspan="1">312 (128–508)</td>
<td align="left" rowspan="1" colspan="1">189 (75–403)</td>
<td align="left" rowspan="1" colspan="1"><0.0001</td>
<td align="left" rowspan="1" colspan="1">450 (270–643)</td>
<td align="left" rowspan="1" colspan="1">476 (272–654)</td>
<td align="left" rowspan="1" colspan="1">0.78</td>
<td align="left" rowspan="1" colspan="1">977 (792–1205)</td>
<td align="left" rowspan="1" colspan="1">861 (741–1008)</td>
<td align="left" rowspan="1" colspan="1">0.23</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">CD8 T-cell count/μL</td>
<td align="left" rowspan="1" colspan="1">832 (564–1336)</td>
<td align="left" rowspan="1" colspan="1">980 (595–1569)</td>
<td align="left" rowspan="1" colspan="1">0.29</td>
<td align="left" rowspan="1" colspan="1">858 (610–1230)</td>
<td align="left" rowspan="1" colspan="1">990 (697–1356)</td>
<td align="left" rowspan="1" colspan="1">0.02</td>
<td align="left" rowspan="1" colspan="1">436 (309–637)</td>
<td align="left" rowspan="1" colspan="1">585 (402–758)</td>
<td align="left" rowspan="1" colspan="1">0.18</td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1">CD4/CD8 ratio</td>
<td align="left" rowspan="1" colspan="1">0.31 (0.17–0.60)</td>
<td align="left" rowspan="1" colspan="1">0.19 (0.09–0.41)</td>
<td align="left" rowspan="1" colspan="1"><0.0001</td>
<td align="left" rowspan="1" colspan="1">0.55 (0.37–0.84)</td>
<td align="left" rowspan="1" colspan="1">0.49 (0.32–0.81)</td>
<td align="left" rowspan="1" colspan="1">0.07</td>
<td align="left" rowspan="1" colspan="1">2.12 (1.70–2.91)</td>
<td align="left" rowspan="1" colspan="1">1.80 (1.01–2.42)</td>
<td align="left" rowspan="1" colspan="1">0.13</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>WBC</bold>
(x1000/μL), mean ± SD</td>
<td align="left" rowspan="1" colspan="1">4.99 ± 1.98</td>
<td align="left" rowspan="1" colspan="1">5.28 ± 2.09</td>
<td align="left" rowspan="1" colspan="1">0.35</td>
<td align="left" rowspan="1" colspan="1">5.0 (4.0–6.0)</td>
<td align="left" rowspan="1" colspan="1">5.0 (4.0–6.0)</td>
<td align="left" rowspan="1" colspan="1">0.90</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>Hemoglobin</bold>
(g/dL), mean ± SD</td>
<td align="left" rowspan="1" colspan="1">11.1 ± 1.79</td>
<td align="left" rowspan="1" colspan="1">10.4 ± 2.02</td>
<td align="left" rowspan="1" colspan="1">0.01</td>
<td align="left" rowspan="1" colspan="1">12.0 (11.0–13.0)</td>
<td align="left" rowspan="1" colspan="1">12.0 (11.0–13.0)</td>
<td align="left" rowspan="1" colspan="1">0.83</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<bold>Platelets</bold>
(x1000/μL), mean ± SD</td>
<td align="left" rowspan="1" colspan="1">262.4 ± 97.2</td>
<td align="left" rowspan="1" colspan="1">314.9 ± 124.2</td>
<td align="left" rowspan="1" colspan="1">0.003</td>
<td align="left" rowspan="1" colspan="1">283 (224–333)</td>
<td align="left" rowspan="1" colspan="1">283 (228–330)</td>
<td align="left" rowspan="1" colspan="1">0.84</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
<td align="left" rowspan="1" colspan="1">NA</td>
</tr>
</tbody>
</table>
</alternatives>
<table-wrap-foot>
<fn id="t003fn001">
<p>Analysis excludes 10 patients with indeterminate
<italic>H</italic>
.
<italic>pylori</italic>
result. BMI, Body mass index; WBC, White blood cells; Hgb, Hemoglobin</p>
</fn>
<fn id="t003fn002">
<p>
<sup>#</sup>
WHO clinical stage at recruitment, missing data for 147 patients of the ART-naïve group and 79 of the ART group.</p>
</fn>
<fn id="t003fn003">
<p>
<sup>
<bold>§</bold>
</sup>
Missing viral load data for 14 H. pylori positive and 17 H. pylori negative participants</p>
</fn>
<fn id="t003fn004">
<p>*Self-reported symptoms in the past 4 weeks, weight loss defined as significant for the patient, or loss of >10% of body weight. Diarrhea was defined as the passage of three or more loose or liquid stools per day</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec013">
<title>Associations between
<italic>H</italic>
.
<italic>pylori</italic>
infection and HIV clinical, immunological and virological parameters</title>
<p>Among ART-naïve HIV patients, those with
<italic>H</italic>
.
<italic>pylori</italic>
co-infection had higher CD4 T cell counts (312 vs. 189 cells/μl, p<0.0001), higher CD4/CD8 ratios (0.31 vs. 0.19, p<0.0001) and lower HIV-1 viral loads (4.92 vs. 5.21 log10 copies/ml, p = 0.006) compared to those without
<italic>H</italic>
.
<italic>pylori</italic>
co-infection.
<italic>H</italic>
.
<italic>pylori</italic>
positive patients in this group also had higher mean hemoglobin levels (11.1 vs. 10.4 g/dl, p = 0.01), and lower platelet counts (262.4 vs. 314.9 x1000/μl, p = 0.003), as shown in
<xref rid="pone.0143388.t003" ref-type="table">Table 3</xref>
. There was no significant difference in the reported use of antibiotics in the 6 months before recruitment between
<italic>H</italic>
.
<italic>pylori</italic>
positive and negative individuals.</p>
<p>
<italic>H</italic>
.
<italic>pylori</italic>
infection was also not associated to increased frequencies of gastrointestinal symptoms in
<italic>H</italic>
.
<italic>pylori</italic>
positive, compared to negative patients, with weight loss (32.6% vs. 40%, p = 0.09), epigastric discomfort (10.0% vs. 9.4%, p = 0.81), and diarrhea (9.6% vs. 9.0%, p = 0.82) being the most common symptoms. In the HIV-infected, ART-exposed group, no significant associations between
<italic>H</italic>
.
<italic>pylori</italic>
status and CD4+ T cell count, HIV-1 viral load, or the proportion of patients with undetectable viral load were observed. However, significantly lower CD8+ T cell counts (858/μL vs. 990/μL, p = 0.02), and a trend towards higher CD4/CD8 ratios (0.55 vs. 0.49, p = 0.07), as possible indicator of decreased immune activation, were noted among those patients with
<italic>H</italic>
.
<italic>pylori</italic>
co-infection [
<xref rid="pone.0143388.ref014" ref-type="bibr">14</xref>
<xref rid="pone.0143388.ref017" ref-type="bibr">17</xref>
].</p>
<p>Among HIV-negative controls, no differences in baseline characteristics, symptoms, or socio-demographic parameters were observed between individuals with and without
<italic>H</italic>
.
<italic>pylori</italic>
infection. A weak trend towards higher CD4/CD8 ratios was also observed in those HIV-negative individuals with
<italic>H</italic>
.
<italic>pylori</italic>
infection, compared to those without
<italic>H</italic>
.
<italic>pylori</italic>
infection (2.12 vs. 1.80, p = 0.13).</p>
<sec id="sec014">
<title>Logistic regression analysis of risk factors associated with H. pylori infection in HIV-positive individuals</title>
<p>Using a logistic multivariable regression model including parameters with p≤0.05 in the univariate analysis and a correlation coefficient of ≤0.1 in the regression model, only CD4+ T cell count (aOR 1.06, 95% CI 1.01–1.12, p = 0.012 for every 100 cells/μl higher) and having access to tap water (aOR 0.63, 95% CI 0.47–0.84, p = 0.002) were associated with
<italic>H</italic>
.
<italic>pylori</italic>
infection (
<xref rid="pone.0143388.t004" ref-type="table">Table 4</xref>
). Significant predictors of
<italic>H</italic>
.
<italic>pylori</italic>
co-infection noted in univariate but not in multivariate analysis included use of anti-tuberculous therapy, current use of ART and use of co-trimoxazole. The risk ratio (RR) for
<italic>H</italic>
.
<italic>pylori</italic>
infection was 0.82 for those patients having access to tap water and 1.37 for those with >200 CD4 T cells/μl within the group of HIV-positive patients. No risk factors were identified to be associated with
<italic>H</italic>
.
<italic>pylori</italic>
infection in the HIV-negative group (data not shown).</p>
<table-wrap id="pone.0143388.t004" orientation="portrait" position="float">
<object-id pub-id-type="doi">10.1371/journal.pone.0143388.t004</object-id>
<label>Table 4</label>
<caption>
<title>Univariate and multivariate logistic regression analysis of factors associated with
<italic>H</italic>
.
<italic>pylori</italic>
co-infection among HIV-infected individuals.</title>
</caption>
<alternatives>
<graphic id="pone.0143388.t004g" xlink:href="pone.0143388.t004"></graphic>
<table frame="hsides" rules="groups">
<colgroup span="1">
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
<col align="left" valign="middle" span="1"></col>
</colgroup>
<thead>
<tr>
<th align="left" rowspan="1" colspan="1">Predictor</th>
<th align="left" rowspan="1" colspan="1">Unadjusted OR (95% CI)</th>
<th align="left" rowspan="1" colspan="1">p-value</th>
<th align="left" rowspan="1" colspan="1">Adjusted OR (95% CI)</th>
<th align="left" rowspan="1" colspan="1">p-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">Female gender</td>
<td align="left" rowspan="1" colspan="1">0.95 (0.71–1.28)</td>
<td align="left" rowspan="1" colspan="1">0.743</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="right" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">-</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Age</td>
<td align="left" rowspan="1" colspan="1">0.10 (0.99–1.01)</td>
<td align="left" rowspan="1" colspan="1">0.968</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">-</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Educational level</td>
<td align="left" rowspan="1" colspan="1">0.94 (0.85–1.03)</td>
<td align="left" rowspan="1" colspan="1">0.167</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">-</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Access to Tap water</td>
<td align="left" rowspan="1" colspan="1">0.69 (0.53–0.89)</td>
<td align="left" rowspan="1" colspan="1">0.005</td>
<td align="left" rowspan="1" colspan="1">0.63 (0.47–0.84)</td>
<td align="left" rowspan="1" colspan="1">0.002</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Intake of tuberculosis therapy</td>
<td align="left" rowspan="1" colspan="1">0.66 (0.43–0.10)</td>
<td align="left" rowspan="1" colspan="1">0.049</td>
<td align="left" rowspan="1" colspan="1">0.72 (0.46–1.12)</td>
<td align="left" rowspan="1" colspan="1">0.142</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Use of co-trimoxazole</td>
<td align="left" rowspan="1" colspan="1">0.74 (0.55–0.10)</td>
<td align="left" rowspan="1" colspan="1">0.046</td>
<td align="left" rowspan="1" colspan="1">0.75 (0.53–1.04)</td>
<td align="left" rowspan="1" colspan="1">0.084</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Use of ART</td>
<td align="left" rowspan="1" colspan="1">1.36 (1.05–1.76)</td>
<td align="left" rowspan="1" colspan="1">0.019</td>
<td align="left" rowspan="1" colspan="1">1.17 (0.86–1.59)</td>
<td align="left" rowspan="1" colspan="1">0.331</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Duration on ART</td>
<td align="left" rowspan="1" colspan="1">1.00 (1.00–1.01)</td>
<td align="left" rowspan="1" colspan="1">0.535</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">-</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">    
<italic>Each 12-month increase</italic>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">T-cell CD4 count</td>
<td align="left" rowspan="1" colspan="1">1.07 (1.03–1.11)</td>
<td align="left" rowspan="1" colspan="1">0.001</td>
<td align="left" rowspan="1" colspan="1">1.06 (1.01–1.12)</td>
<td align="left" rowspan="1" colspan="1">0.012</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">    
<italic>Each increase of 100 cells/</italic>
μ
<italic>L</italic>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Viral load</td>
<td align="left" rowspan="1" colspan="1">0.91 (0.86–0.98)</td>
<td align="left" rowspan="1" colspan="1">0.007</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">-</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">    
<italic>Each increase of 1 log c/mL</italic>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
</alternatives>
<table-wrap-foot>
<fn id="t004fn001">
<p>Parameters with a p-value ≤0.05 and a correlation coefficient of ≤0.1 between the parameters were included into the multivariate regression model.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
</sec>
</sec>
<sec sec-type="conclusions" id="sec015">
<title>Discussion</title>
<p>This is the first and largest study to systematically investigate the interplay between
<italic>H</italic>
.
<italic>pylori</italic>
and HIV infection in sub-Saharan Africa, where both infections are highly co-endemic. We assessed the prevalence of
<italic>H</italic>
.
<italic>pylori</italic>
co-infection in a large cohort of unselected adult HIV-infected individuals and HIV-negative controls, and its association with clinical, immunological and virological parameters. We found a graded decrease in
<italic>H</italic>
.
<italic>pylori</italic>
prevalence in relation to the level of immune competence, being 88% in HIV-negative and 51.5% in HIV-positive individuals. Among HIV positive individuals,
<italic>H</italic>
.
<italic>pylori</italic>
prevalence declined in tandem with CD4+ T cell counts. A similar trend was observed in HIV-negative individuals, although statistical significance was not attained.</p>
<p>Our results are in accordance with previous epidemiologic studies, indicating a lower
<italic>H</italic>
.
<italic>pylori</italic>
prevalence in HIV-positive compared to HIV-negative individuals, and also among patients with AIDS compared to matched HIV-infected patients without AIDS [
<xref rid="pone.0143388.ref001" ref-type="bibr">1</xref>
,
<xref rid="pone.0143388.ref002" ref-type="bibr">2</xref>
]. However, the interpretation of existing studies is hampered by important limitations, such as small sample sizes which precluded subgroup analyses, and heterogeneous study populations, often including only patients with gastrointestinal symptoms [
<xref rid="pone.0143388.ref002" ref-type="bibr">2</xref>
]. Information on socio-demographic variables, as putative confounders for
<italic>H</italic>
.
<italic>pylori</italic>
status, often lacking in previous studies have been explored in the present study. Furthermore, studies including asymptomatic patients used serological tests to determine
<italic>H</italic>
.
<italic>pylori</italic>
status, which have been shown to be problematic especially in HIV-infected individuals [
<xref rid="pone.0143388.ref018" ref-type="bibr">18</xref>
].
<italic>H</italic>
.
<italic>pylori</italic>
stool antigen tests, as employed in the present study, are non-invasive and have a proven high sensitivity and specificity, making them suitable tools for epidemiologic studies including HIV-infected individuals [
<xref rid="pone.0143388.ref012" ref-type="bibr">12</xref>
,
<xref rid="pone.0143388.ref013" ref-type="bibr">13</xref>
].</p>
<p>Although
<italic>H</italic>
.
<italic>pylori</italic>
is generally considered a disease of poverty and known to be associated with poor hygienic conditions, HIV-negative participants in our study, having a clearly higher
<italic>H</italic>
.
<italic>pylori</italic>
prevalence, ironically had indicators of a higher socioeconomic status. This suggests that the significant differences in
<italic>H</italic>
.
<italic>pylori</italic>
prevalence observed between the HIV positive and HIV negative participants may not be explained wholly by socioeconomic disparities. Indeed, the HIV negative participants had more frequent access to tap water compared to HIV-positive individuals, and having no access to tap water was independently associated with the
<italic>H</italic>
.
<italic>pylori</italic>
infection in our study. Besides indicating poor sanitary conditions, the lack of access to tap water might also directly promote
<italic>H</italic>
.
<italic>pylori</italic>
acquisition by consumption of contaminated drinking water, e.g. from wells. An association between
<italic>H</italic>
.
<italic>pylori</italic>
and the consumption of water from wells has previously been reported from India, [
<xref rid="pone.0143388.ref019" ref-type="bibr">19</xref>
] and
<italic>H</italic>
.
<italic>pylori</italic>
has also been identified in drinking water samples from Pakistan by PCR [
<xref rid="pone.0143388.ref020" ref-type="bibr">20</xref>
].</p>
<p>We also found a significant graded decrease in
<italic>H</italic>
.
<italic>pylori</italic>
prevalence with the progression of immunodeficiency in HIV-positive individuals, with the same trend being observed in HIV-negative individuals, but without reaching statistical significance. The underlying mechanisms responsible for this association between immune competence and
<italic>H</italic>
.
<italic>pylori</italic>
prevalence are still unclear, although several hypotheses have been offered [
<xref rid="pone.0143388.ref002" ref-type="bibr">2</xref>
]. The most popular is that more frequent bacterial infections in HIV patients, especially those with advanced disease stages, lead to antibiotic treatment courses, probably resulting in unintended
<italic>H</italic>
.
<italic>pylori</italic>
eradication [
<xref rid="pone.0143388.ref002" ref-type="bibr">2</xref>
]. We found no association between
<italic>H</italic>
.
<italic>pylori</italic>
status and reported intake of antibiotics in the past six months before recruitment. Furthermore, only few patients reported taking antibiotics in this period of time, making it unlikely that the observed differences in
<italic>H</italic>
.
<italic>pylori</italic>
prevalence are explained by unintended eradication in our study population.</p>
<p>Antibiotic monotherapy has been reported to have only minor efficacy in
<italic>H</italic>
.
<italic>pylori</italic>
eradication [
<xref rid="pone.0143388.ref021" ref-type="bibr">21</xref>
]. Using a meta-analysis methodology, a pooled
<italic>H</italic>
.
<italic>pylori</italic>
eradication rate of 19% for monotherapy regimens has been reported [
<xref rid="pone.0143388.ref022" ref-type="bibr">22</xref>
]. In our study, Co-trimoxazole prophylaxis and tuberculosis therapy were associated with lower risk of
<italic>H</italic>
.
<italic>pylori</italic>
status in univariate, but not in multivariate logistic regression analysis. Co-trimoxazole has not been reported to have activity against
<italic>H</italic>
.
<italic>pylori</italic>
, and a culture medium containing trimethoprim and sulfamethoxazole has been developed to selectively isolate
<italic>H</italic>
.
<italic>pylori</italic>
from animal samples [
<xref rid="pone.0143388.ref023" ref-type="bibr">23</xref>
]. In contrast, it is known that rifampicin has activity against
<italic>H</italic>
.
<italic>pylori</italic>
[
<xref rid="pone.0143388.ref024" ref-type="bibr">24</xref>
]. A temporary suppression of
<italic>H</italic>
.
<italic>pylori</italic>
replication by concurrent tuberculosis treatment, or even clearance of the infection, is thus conceivable. However, it is to be noted that HIV patients with advanced disease are often prescribed Co-trimoxazole prophylaxis against opportunistic infections and are also more likely to receive anti-tubercular therapy for tuberculosis hence the observed lack of significant association in multivariate analyses between use of these antibiotics and risk of
<italic>H</italic>
.
<italic>pylori</italic>
co-infection. These findings suggest that progressive HIV disease rather than antibiotic usage may account for the diminution in frequency of
<italic>H</italic>
.
<italic>pylori</italic>
co-infection.</p>
<p>Another proposed hypothesis is that the maintenance of
<italic>H</italic>
.
<italic>pylori</italic>
infection requires an intact mucosal cellular immunity, and that the loss of the CD4+ T cell population in the gastric mucosa may prevent
<italic>H</italic>
.
<italic>pylori</italic>
persistence [
<xref rid="pone.0143388.ref002" ref-type="bibr">2</xref>
,
<xref rid="pone.0143388.ref025" ref-type="bibr">25</xref>
,
<xref rid="pone.0143388.ref026" ref-type="bibr">26</xref>
]. Hence the parallel decline of
<italic>H</italic>
.
<italic>pylori</italic>
prevalence with CD4+ T cell count would be consistent with this theory, although there is no evidence that impaired T cell immunity itself might cause a loss of
<italic>H</italic>
.
<italic>pylori</italic>
infection. CD4+ T cells have been shown to be increased in
<italic>H</italic>
.
<italic>pylori</italic>
gastritis, but gastric inflammation has been shown to correlate with lower
<italic>H</italic>
.
<italic>pylori</italic>
bacterial load, and pro-inflammatory genetic profiles are associated to lower
<italic>H</italic>
.
<italic>pylori</italic>
seroprevalence [
<xref rid="pone.0143388.ref027" ref-type="bibr">27</xref>
<xref rid="pone.0143388.ref029" ref-type="bibr">29</xref>
]. While Th1 and Th17-polarized effector T cell subsets are critical for the control of
<italic>H</italic>
.
<italic>pylori</italic>
infection, regulatory T cells have the ability to override this T cell driven immunity [
<xref rid="pone.0143388.ref030" ref-type="bibr">30</xref>
]. Although the alterations of gastric mucosal T cell immunity in the context of HIV infection are incompletely understood, HIV infection apparently rather impairs regulatory T cell suppressive capacity and is thus unlikely to directly promote
<italic>H</italic>
.
<italic>pylori</italic>
persistence [
<xref rid="pone.0143388.ref031" ref-type="bibr">31</xref>
]. Further studies are needed to dissect the interplay between systemic and local mucosal T-cell immunity and
<italic>H</italic>
.
<italic>pylori</italic>
persistence in the context of HIV infection.</p>
<p>
<italic>H</italic>
.
<italic>pylori</italic>
infection is linked to a number of adverse clinical effects, such as iron deficiency anemia, childhood growth faltering, other gastrointestinal infections and chronic diarrhea[
<xref rid="pone.0143388.ref032" ref-type="bibr">32</xref>
<xref rid="pone.0143388.ref035" ref-type="bibr">35</xref>
]. In our study however,
<italic>H</italic>
.
<italic>pylori</italic>
infection was not associated to the presence of diarrhea, anemia, malnutrition or parasitic diseases (data not shown). Indeed a paradoxical protective effect of
<italic>H</italic>
.
<italic>pylori</italic>
infection against tuberculosis has been reported [
<xref rid="pone.0143388.ref036" ref-type="bibr">36</xref>
]. Furthermore,
<italic>H</italic>
.
<italic>pylori</italic>
infection is associated with enhanced Th1-type immune responses to TB antigens [
<xref rid="pone.0143388.ref037" ref-type="bibr">37</xref>
]. We have recently shown that
<italic>H</italic>
.
<italic>pylori</italic>
infection is associated with decreased markers of immune activation in ART-naïve HIV infected patients [
<xref rid="pone.0143388.ref038" ref-type="bibr">38</xref>
]. Considering that immune activation has been demonstrated to be one of the key mechanisms in HIV pathogenesis [
<xref rid="pone.0143388.ref014" ref-type="bibr">14</xref>
<xref rid="pone.0143388.ref017" ref-type="bibr">17</xref>
], it is tempting to speculate that
<italic>H</italic>
.
<italic>pylori</italic>
infection may influence susceptibility to HIV infection or the natural course of HIV disease. A large proportion of HIV-infected individuals worldwide are co-infected with
<italic>H</italic>
.
<italic>pylori</italic>
, hence such interaction could be relevant for the understanding of HIV immunopathology, and could also have public health implications, especially considering the ongoing efforts to develop an
<italic>H</italic>
.
<italic>pylori</italic>
vaccine [
<xref rid="pone.0143388.ref039" ref-type="bibr">39</xref>
].</p>
<p>There are some limitations of our study to be mentioned. The sample size of our HIV-negative group was smaller than that of HIV-positive individuals, and differed in terms of age and gender distribution. However, the main focus of this study was to analyze the effect of
<italic>H</italic>
.
<italic>pylori</italic>
within the group of HIV patients. Since we included unselected HIV patients, the group was heterogenous, among others, in terms of ART status and clinical stage of HIV disease. The group of patients taking ART in particular was heterogeneous, and we did not record details on the history and efficacy of ART in terms of CD4+ T cell recovery and virological suppression, limiting the informative value of the analysis in this subgroup. Importantly, the cross sectional study design did not allow for the investigation of causal relationships concerning the described associations.</p>
<p>In conclusion, we have shown that
<italic>H</italic>
.
<italic>pylori</italic>
infection is associated with higher CD4+ T cell counts and lower HIV-1 viral loads in ART-naïve patients. Our findings could not be explained by typical confounders as socioeconomic factors, time since diagnosis of HIV infection or unintended
<italic>H</italic>
.
<italic>pylori</italic>
eradication by antibiotic use for other infectious conditions. Considering the pathophysiological overlap of both chronic infections, the effects of
<italic>H</italic>
.
<italic>pylori</italic>
infection on the systemic immune response, and subsequently on the natural course of HIV disease, warrants further investigation employing prospective studies.</p>
</sec>
<sec sec-type="supplementary-material" id="sec016">
<title>Supporting Information</title>
<supplementary-material content-type="local-data" id="pone.0143388.s001">
<label>S1 Table</label>
<caption>
<title>Comparison of demographic, clinical and laboratory characteristics of HIV positive participants according to ART status.</title>
<p>(DOCX)</p>
</caption>
<media xlink:href="pone.0143388.s001.docx">
<caption>
<p>Click here for additional data file.</p>
</caption>
</media>
</supplementary-material>
</sec>
</body>
<back>
<ack>
<p>We are grateful to the nurses and physicians of the HIV clinic and the blood bank of the Komfo Anokye Teaching Hospital in Kumasi, Ghana for their support and Mr. Shadrack Osei Assibey for data entry. We thank ESTHER Germany for their continuous support of the partnership with the Komfo Anokye Teaching Hospital.</p>
</ack>
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