Clinic-Based Urinary Lipoarabinomannan as a Biomarker of Clinical Disease Severity and Mortality Among Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Infected Adults in South Africa
Identifieur interne : 000A37 ( Main/Exploration ); précédent : 000A36; suivant : 000A38Clinic-Based Urinary Lipoarabinomannan as a Biomarker of Clinical Disease Severity and Mortality Among Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Infected Adults in South Africa
Auteurs : Paul K. Drain ; Elena Losina ; Sharon M. Coleman ; Janet Giddy [Afrique du Sud] ; Douglas Ross [Afrique du Sud] ; Jeffrey N. Katz ; Kenneth A. Freedberg ; Ingrid V. BassettSource :
- Open Forum Infectious Diseases [ 2328-8957 ] ; 2017.
Abstract
Urinary lipoarabinomannan (LAM) has limited sensitivity for diagnosing active human immunodeficiency virus (HIV)-associated tuberculosis (TB) disease, but LAM screening at HIV diagnosis might identify adults with more severe clinical disease or greater risk of mortality.
We enrolled antiretroviral therapy-naive HIV-infected adults from 4 clinics in Durban. Nurses performed urine LAM testing using a rapid assay (Determine TB LAM) graded from low (1+) to high (≥3+) intensity. Urine LAM results were not used to guide anti-TB therapy. We assessed TB-related symptoms and obtained sputum for mycobacterial smear and culture. Participants were observed for 12 months, and we used multivariable Cox proportional hazard models to determine hazard ratios for all-cause mortality.
Among 726 HIV-infected adults with median CD4 of 205 cells/mm3 (interquartile range, 79–350 cells/mm3), 93 (13%) were LAM positive and 89 (12%) participants died during the follow-up period. In multivariable analyses, urine LAM-positive participants had a mortality hazard ratio (MHR) of 3.58 (95% confidence interval [CI], 2.20–5.81) for all-cause mortality. Among participants with mycobacterial-confirmed TB, urine LAM-positivity had a 2.91 (95% CI, 1.26–6.73) MHR for all participants and a 4.55 (95% CI, 1.71–12.1) MHR for participants with CD4 ≤100 cell/mm3. Participants with LAM-positive TB had significantly more clinical signs and symptoms of disease, compared with participants with LAM-negative TB disease.
Among HIV-infected adults, urinary LAM-positive patients had more clinical disease severity and a 3-fold increase in 12-month mortality compared with those who were LAM negative.
Url:
DOI: 10.1093/ofid/ofx167
PubMed: 28979922
PubMed Central: 5622366
Affiliations:
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Drain</name><affiliation><nlm:aff id="AF0001"><institution>Departments of Global Health</institution>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="AF0002"><institution>Medicine</institution></nlm:aff></affiliation><affiliation><nlm:aff id="AF0003"><institution>Epidemiology, University of Washington</institution>,<addr-line>Seattle</addr-line>;<institution>Departments of</institution></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="AF0004"><institution>Surgery</institution></nlm:aff></affiliation></author><author><name sortKey="Losina, Elena" sort="Losina, Elena" uniqKey="Losina E" first="Elena" last="Losina">Elena Losina</name><affiliation><nlm:aff id="AF0006"><institution>Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School</institution>,<addr-line>Boston</addr-line>,<addr-line>Massachussetts</addr-line>;</nlm:aff></affiliation><affiliation><nlm:aff id="AF0007"><institution>Boston University School of Public Health</institution>,<addr-line>Massachussetts</addr-line>;</nlm:aff></affiliation></author><author><name sortKey="Coleman, Sharon M" sort="Coleman, Sharon M" uniqKey="Coleman S" first="Sharon M" last="Coleman">Sharon M. 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Drain</name><affiliation><nlm:aff id="AF0001"><institution>Departments of Global Health</institution>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="AF0002"><institution>Medicine</institution></nlm:aff></affiliation><affiliation><nlm:aff id="AF0003"><institution>Epidemiology, University of Washington</institution>,<addr-line>Seattle</addr-line>;<institution>Departments of</institution></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="AF0004"><institution>Surgery</institution></nlm:aff></affiliation></author><author><name sortKey="Losina, Elena" sort="Losina, Elena" uniqKey="Losina E" first="Elena" last="Losina">Elena Losina</name><affiliation><nlm:aff id="AF0006"><institution>Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School</institution>,<addr-line>Boston</addr-line>,<addr-line>Massachussetts</addr-line>;</nlm:aff></affiliation><affiliation><nlm:aff id="AF0007"><institution>Boston University School of Public Health</institution>,<addr-line>Massachussetts</addr-line>;</nlm:aff></affiliation></author><author><name sortKey="Coleman, Sharon M" sort="Coleman, Sharon M" uniqKey="Coleman S" first="Sharon M" last="Coleman">Sharon M. Coleman</name><affiliation><nlm:aff id="AF0007"><institution>Boston University School of Public Health</institution>,<addr-line>Massachussetts</addr-line>;</nlm:aff></affiliation></author><author><name sortKey="Giddy, Janet" sort="Giddy, Janet" uniqKey="Giddy J" first="Janet" last="Giddy">Janet Giddy</name><affiliation wicri:level="1"><nlm:aff id="AF0008"><institution>Department of Medicine, McCord Hospital</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country>;</nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ross, Douglas" sort="Ross, Douglas" uniqKey="Ross D" first="Douglas" last="Ross">Douglas Ross</name><affiliation wicri:level="1"><nlm:aff id="AF0009"><institution>Department of Medicine, St. Mary’s Hospital</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Katz, Jeffrey N" sort="Katz, Jeffrey N" uniqKey="Katz J" first="Jeffrey N" last="Katz">Jeffrey N. Katz</name><affiliation><nlm:aff id="AF0006"><institution>Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School</institution>,<addr-line>Boston</addr-line>,<addr-line>Massachussetts</addr-line>;</nlm:aff></affiliation></author><author><name sortKey="Freedberg, Kenneth A" sort="Freedberg, Kenneth A" uniqKey="Freedberg K" first="Kenneth A" last="Freedberg">Kenneth A. Freedberg</name><affiliation><nlm:aff id="AF0005"><institution>Medicine</institution>,<institution>Massachusetts General Hospital, Harvard Medical School</institution>,<addr-line>Boston</addr-line>;</nlm:aff></affiliation><affiliation><nlm:aff id="AF0007"><institution>Boston University School of Public Health</institution>,<addr-line>Massachussetts</addr-line>;</nlm:aff></affiliation></author><author><name sortKey="Bassett, Ingrid V" sort="Bassett, Ingrid V" uniqKey="Bassett I" first="Ingrid V" last="Bassett">Ingrid V. Bassett</name><affiliation><nlm:aff id="AF0005"><institution>Medicine</institution>,<institution>Massachusetts General Hospital, Harvard Medical School</institution>,<addr-line>Boston</addr-line>;</nlm:aff></affiliation></author></analytic><series><title level="j">Open Forum Infectious Diseases</title><idno type="eISSN">2328-8957</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><sec id="s1"><title>Background</title><p>Urinary lipoarabinomannan (LAM) has limited sensitivity for diagnosing active human immunodeficiency virus (HIV)-associated tuberculosis (TB) disease, but LAM screening at HIV diagnosis might identify adults with more severe clinical disease or greater risk of mortality.</p></sec><sec id="s2"><title>Methods</title><p>We enrolled antiretroviral therapy-naive HIV-infected adults from 4 clinics in Durban. Nurses performed urine LAM testing using a rapid assay (Determine TB LAM) graded from low (1+) to high (≥3+) intensity. Urine LAM results were not used to guide anti-TB therapy. We assessed TB-related symptoms and obtained sputum for mycobacterial smear and culture. Participants were observed for 12 months, and we used multivariable Cox proportional hazard models to determine hazard ratios for all-cause mortality.</p></sec><sec id="s3"><title>Results</title><p>Among 726 HIV-infected adults with median CD4 of 205 cells/mm<sup>3</sup> (interquartile range, 79–350 cells/mm<sup>3</sup>), 93 (13%) were LAM positive and 89 (12%) participants died during the follow-up period. In multivariable analyses, urine LAM-positive participants had a mortality hazard ratio (MHR) of 3.58 (95% confidence interval [CI], 2.20–5.81) for all-cause mortality. Among participants with mycobacterial-confirmed TB, urine LAM-positivity had a 2.91 (95% CI, 1.26–6.73) MHR for all participants and a 4.55 (95% CI, 1.71–12.1) MHR for participants with CD4 ≤100 cell/mm<sup>3</sup>. Participants with LAM-positive TB had significantly more clinical signs and symptoms of disease, compared with participants with LAM-negative TB disease.</p></sec><sec id="s4"><title>Conclusions</title><p>Among HIV-infected adults, urinary LAM-positive patients had more clinical disease severity and a 3-fold increase in 12-month mortality compared with those who were LAM negative.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Getahun, H" uniqKey="Getahun H">H Getahun</name></author><author><name sortKey="Kittikraisak, W" uniqKey="Kittikraisak W">W Kittikraisak</name></author><author><name sortKey="Heilig, Cm" uniqKey="Heilig C">CM Heilig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Denkinger, Cm" uniqKey="Denkinger C">CM. Denkinger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Denkinger, Cm" uniqKey="Denkinger C">CM Denkinger</name></author><author><name sortKey="Kik, Sv" uniqKey="Kik S">SV Kik</name></author><author><name sortKey="Cirillo, Dm" uniqKey="Cirillo D">DM Cirillo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lawn, Sd" uniqKey="Lawn S">SD Lawn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gupta Wright, A" uniqKey="Gupta Wright A">A Gupta-Wright</name></author><author><name sortKey="Peters, Ja" uniqKey="Peters J">JA Peters</name></author><author><name sortKey="Flach, C" uniqKey="Flach C">C Flach</name></author><author><name sortKey="Lawn, Sd" uniqKey="Lawn S">SD Lawn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drain, Pk" uniqKey="Drain P">PK Drain</name></author><author><name sortKey="Losina, E" uniqKey="Losina E">E Losina</name></author><author><name sortKey="Coleman, Sm" uniqKey="Coleman S">SM Coleman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drain, Pk" uniqKey="Drain P">PK Drain</name></author><author><name sortKey="Losina, E" uniqKey="Losina E">E Losina</name></author><author><name sortKey="Coleman, Sm" uniqKey="Coleman S">SM Coleman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lawn, Sd" uniqKey="Lawn S">SD Lawn</name></author><author><name sortKey="Kerkhoff, Ad" uniqKey="Kerkhoff A">AD Kerkhoff</name></author><author><name sortKey="Vogt, M" uniqKey="Vogt M">M Vogt</name></author><author><name sortKey="Wood, R" uniqKey="Wood R">R Wood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bjerrum, S" uniqKey="Bjerrum S">S Bjerrum</name></author><author><name sortKey="Kenu, E" uniqKey="Kenu E">E Kenu</name></author><author><name sortKey="Lartey, M" uniqKey="Lartey M">M Lartey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Balcha, Tt" uniqKey="Balcha T">TT Balcha</name></author><author><name sortKey="Winqvist, N" uniqKey="Winqvist N">N Winqvist</name></author><author><name sortKey="Stureg Rd, E" uniqKey="Stureg Rd E">E Sturegård</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, Iv" uniqKey="Bassett I">IV Bassett</name></author><author><name sortKey="Giddy, J" uniqKey="Giddy J">J Giddy</name></author><author><name sortKey="Chaisson, Ce" uniqKey="Chaisson C">CE Chaisson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, Iv" uniqKey="Bassett I">IV Bassett</name></author><author><name sortKey="Coleman, Sm" uniqKey="Coleman S">SM Coleman</name></author><author><name sortKey="Giddy, J" uniqKey="Giddy J">J Giddy</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Peter, Jg" uniqKey="Peter J">JG Peter</name></author><author><name sortKey="Zijenah, Ls" uniqKey="Zijenah L">LS Zijenah</name></author><author><name sortKey="Chanda, D" uniqKey="Chanda D">D Chanda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lawn, Sd" uniqKey="Lawn S">SD Lawn</name></author><author><name sortKey="Kerkhoff, Ad" uniqKey="Kerkhoff A">AD Kerkhoff</name></author><author><name sortKey="Burton, R" uniqKey="Burton R">R Burton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peter, J" uniqKey="Peter J">J Peter</name></author><author><name sortKey="Theron, G" uniqKey="Theron G">G Theron</name></author><author><name sortKey="Chanda, D" uniqKey="Chanda D">D Chanda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Manabe, Yc" uniqKey="Manabe Y">YC Manabe</name></author><author><name sortKey="Nonyane, Ba" uniqKey="Nonyane B">BA Nonyane</name></author><author><name 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Grobler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drain, Pk" uniqKey="Drain P">PK Drain</name></author><author><name sortKey="Gounder, L" uniqKey="Gounder L">L Gounder</name></author><author><name sortKey="Sahid, F" uniqKey="Sahid F">F Sahid</name></author><author><name sortKey="Moosa, My" uniqKey="Moosa M">MY Moosa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fielding, Kl" uniqKey="Fielding K">KL Fielding</name></author><author><name sortKey="Charalambous, S" uniqKey="Charalambous S">S Charalambous</name></author><author><name sortKey="Hoffmann, Cj" uniqKey="Hoffmann C">CJ Hoffmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tlali, M" uniqKey="Tlali M">M Tlali</name></author><author><name sortKey="Charalambous, S" uniqKey="Charalambous S">S Charalambous</name></author><author><name sortKey="Fielding, K" uniqKey="Fielding K">K Fielding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hamasur, B" uniqKey="Hamasur B">B Hamasur</name></author><author><name sortKey="Bruchfeld, J" uniqKey="Bruchfeld J">J Bruchfeld</name></author><author><name sortKey="Van Helden, P" uniqKey="Van Helden P">P van Helden</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Afrique du Sud</li></country></list><tree><noCountry><name sortKey="Bassett, Ingrid V" sort="Bassett, Ingrid V" uniqKey="Bassett I" first="Ingrid V" last="Bassett">Ingrid V. Bassett</name><name sortKey="Coleman, Sharon M" sort="Coleman, Sharon M" uniqKey="Coleman S" first="Sharon M" last="Coleman">Sharon M. Coleman</name><name sortKey="Drain, Paul K" sort="Drain, Paul K" uniqKey="Drain P" first="Paul K." last="Drain">Paul K. Drain</name><name sortKey="Freedberg, Kenneth A" sort="Freedberg, Kenneth A" uniqKey="Freedberg K" first="Kenneth A" last="Freedberg">Kenneth A. Freedberg</name><name sortKey="Katz, Jeffrey N" sort="Katz, Jeffrey N" uniqKey="Katz J" first="Jeffrey N" last="Katz">Jeffrey N. Katz</name><name sortKey="Losina, Elena" sort="Losina, Elena" uniqKey="Losina E" first="Elena" last="Losina">Elena Losina</name></noCountry><country name="Afrique du Sud"><noRegion><name sortKey="Giddy, Janet" sort="Giddy, Janet" uniqKey="Giddy J" first="Janet" last="Giddy">Janet Giddy</name></noRegion><name sortKey="Ross, Douglas" sort="Ross, Douglas" uniqKey="Ross D" first="Douglas" last="Ross">Douglas Ross</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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