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J Infect Dis. 2009 Sep 15;200(6):973-83. doi: 10.1086/605447.

Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection.

Collaborators (747)

Lundgren JD, Jensen KB, Gey DC, Borup L, Pearson M, Jansson PO, Jensen BG, Tverland J, Juncker-Benzon H, Fox Z, Phillips AN, Darbyshire JH, Babiker AG, Palfreeman AJ, Fleck SL, Dodds W, King E, Cordwell B, van Hooff F, Collaco-Moraes Y, Cooper DA, Emery S, Drummond FM, Connor SA, Satchell S, Gunn S, Oka S, Delfino MA, Merlin K, McGinley C, Gordin F, Finley E, Dietz D, Chesson C, Vjecha M, Standridge B, Neaton JD, Bartsch G, DuChene A, George M, Grund B, Harrison M, Krum E, Larson G, Miller C, Nelson R, Neuhaus J, Roediger MP, Schultz T, Prineas R, Campbell C, Zhang ZM, Perez G, Lifson A, Duprez D, Hoy J, Lahart C, Perlman D, Price R, Prineas R, Rhame F, Sampson J, Worley J, Rein M, DerSimonian R, Brody BA, Daar ES, Dubler NN, Fleming TR, Freeman DJ, Kahn JP, Kim KM, Medoff G, Modlin JF, Moellering R Jr, Murray BE, Pick B, Robb ML, Scharfstein DO, Sugarman J, Tsiatis A, Tuazon C, Zoloth L, Klingman K, Lehrman S, Lazovski J, Belloso WH, Losso MH, Benetucci JA, Aquilia S, Bittar V, Bogdanowicz EP, Cahn CE, Casiró AD, Cassetti I, Contarelli JM, Corral JA, Crinejo A, Daciuk L, David O, Guaragna G, Ishida MT, Krolewiecki A, Laplume HE, Lasala MB, Lourtau L, Lupo SH, Maranzana A, Masciottra F, Michaan M, Ruggieri L, Salazar E, Sánchez M, Somenzini C, Hoy JF, Rogers GD, Allworth AM, Anderson JS, Armishaw J, Barnes K, Carr A, Chiam A, Chuah JC, Curry MC, Dever RL, Donohue WA, Doong NC, Dwyer DE, Dyer J, Eu B, Ferguson VW, French MA, Garsia RJ, Gold J, Hudson JH, Jeganathan S, Konecny P, Leung J, McCormack CL, McMurchie M, Medland N, Moore RJ, Moussa MB, Orth D, Piper M, Read T, Roney JJ, Roth N, Shaw DR, Silvers J, Smith DJ, Street AC, Vale RJ, Wendt NA, Wood H, Youds DW, Zillman J, Rieger A, Tozeau V, Aichelburg A, Vetter N, Clumeck N, Dewit S, de Roo A, Kabeya K, Leonard P, Lynen L, Moutschen M, O'Doherty E, Pereira LC Jr, Souza TN, Schechter M, Zajdenverg R, Almeida MM, Araujo F, Bahia F, Brites C, Caseiro MM, Casseb J, Etzel A, Falco GG, Filho EC, Flint SR, Gonzales CR, Madruga JV, Passos LN, Reuter T, Sidi LC, Toscano AL, Zarowny D, Cherban E, Cohen J, Conway B, Dufour C, Ellis M, Foster A, Haase D, Haldane H, Houde M, Kato C, Klein M, Lessard B, Martel A, Martel C, McFarland N, Paradis E, Piche A, Sandre R, Schlech W, Schmidt S, Smaill F, Thompson B, Trottier S, Vezina S, Walmsley, Wolff Reyes MJ, Northland R, Ostergaard L, Pedersen C, Nielsen H, Hergens L, Loftheim IR, Jensen KB, Raukas M, Zilmer K, Justinen J, Ristola M, Girard PM, Landman R, Abel S, Abgrall S, Amat K, Auperin L, Barruet R, Benalycherif A, Benammar N, Bensalem M, Bentata M, Besnier JM, Blanc M, Bouchaud O, Cabié A, Chavannet P, Chennebault JM, Dargere S, de la Tribonniere X, Debord T, Decaux N, Delgado J, Dupon M, Durant J, Frixon-Marin V, Genet C, Gérard L, Gilquin J, Hoen B, Jeantils V, Kouadio H, Leclercq P, Lelièvre JD, Levy Y, Michon CP, Nau P, Pacanowski J, Piketty C, Poizot-Martin I, Raymond I, Salmon D, Schmit JL, Serini MA, Simon A, Tassi S, Touam F, Verdon R, Weinbreck P, Weiss L, Yazdanpanah Y, Yeni P, Fätkenheuer G, Staszewski S, Bergmann F, Bitsch S, Bogner JR, Brockmeyer N, Esser S, Goebel FD, Hartmann M, Klinker H, Lehmann C, Lennemann, Plettenberg A, Potthof A, Rockstroh B, Ross B, Stoehr A, Wasmuth JC, Wiedemeyer K, Winzer R, Hatzakis A, Touloumi G, Antoniadou A, Daikos GL, Dimitrakaki A, Gargalianos-Kakolyris P, Giannaris M, Karafoulidou A, Katsambas A, Katsarou O, Kontos AN, Kordossis T, Lazanas MK, Panagopoulos P, Panos G, Paparizos V, Papastamopoulos V, Petrikkos G, Sambatakou H, Skoutelis A, Tsogas N, Xylomenos G, Bergin CJ, Mooka B, Pollack S, Mamorksy MG, Agmon-Levin N, Karplus R, Kedem E, Maayan S, Shahar E, Sthoeger Z, Turner D, Yust I, Tambussi G, Rusconi V, Abeli C, Bechi M, Biglino A, Bonora S, Butini L, Cariso G, Casari S, Corpolongo A, De Gioanni M, Di Perri G, Di Pietro M, D'Offizi G, Esposito R, Mazzotta F, Montroni M, Nardini G, Nozza S, Quirino T, Raise E, Honda M, Ishisaka M, Caplinskas S, Uzdaviniene V, Schmit JC, Staub T, Himmich H, Marhoum El Filali K, Mills GD, Blackmore T, Masters JA, Morgan J, Pithie A, Brunn J, Ormasssen V, La Rosa A, Guerra O, Espichan M, Gutierrez L, Mendo F, Salazar R, Knytz B, Horban A, Bakowska E, Beniowski M, Gasiorowski J, Kwiatkowski J, Antunes F, Castro RS, Doroana M, Horta A, Mansinho K, Miranda AC, Pinto IV, Valadas E, Vera J, Rakhmanova A, Vinogradova E, Yakovlev A, Zakharova N, Wood R, Orrel C, Gatell J, Arnaiz JA, Carrillo R, Clotet B, Dalmau D, González A, Jordano Q, Jou A, Knobel H, Larrousse M, Mata R, Moreno JS, Oretaga E, Pena JN, Pulido F, Rubio R, Sanz J, Viciana P, Hirschel B, Spycher R, Battegay M, Bernasconi E, Bottone S, Cavassini M, Christen A, Franc C, Furrer HJ, Gayet-Ageron A, Genné D, Hochstrasser S, Magenta L, Moens C, Müller N, Nüesch R, Phanuphak P, Ruxrungtham K, Pumpradit W, Chetchotisakd P, Dangthongdee S, Kiertiburanakul S, Klinbuayaem V, Mootsikapun P, Nonenoy S, Piyavong B, Prasithsirikul W, Raksakulkarn P, Gazzard BG, Ainsworth JG, Anderson J, Angus BJ, Barber TJ, Brook MG, Care CD, Chadwick DR, Chikohora M, Churchill DR, Cornforth D, Dockrell DH, Easterbrook PJ, Fox PA, Fox R, Gomez PA, Gompels MM, Harris GM, Herman, Jackson AG, Jebakumar SP, Johnson MA, Kinghorn GR, Kuldanek KA, Larbalestier N, Leen C, Lumsden M, Maher T, Mantell J, Maw R, McKernan S, McLean L, Morris S, Muromba L, Orkin CM, Palfreeman AJ, Peters BS, Peto TE, Portsmouth SD, Rajamanoharan S, Ronan S, Schwenk A, Slinn MA, Stroud CJ, Thomas RC, Wansbrough-Jones MH, Whiles HJ, White DJ, Williams E, Williams IG, Youle M, Abrams DI, Acosta EA, Adams S, Adamski A, Andrews L, Antoniskis D, Aragon DR, Arduino R, Artz R, Bailowitz J, Barnett BJ, Baroni C, Barron M, Baxter JD, Beers D, Beilke M, Bemenderfer D, Bernard A, Besch CL, Bessesen MT, Bethel JT, Blue S, Blum JD, Boarden S, Bolan RK, Borgman JB, Brar I, Braxton BK, Bredeek UF, Brennan R, Britt DE, Brockelman J, Brown S, Bruzzese V, Bulgin-Coleman D, Bullock DE, Cafaro V, Campbell B, Caras S, Carroll J, Casey KK, Chiang F, Childress G, Cindrich RB, Clark C, Climo M, Cohen C, Coley J, Condoluci DV, Contreras R, Corser J, Cozzolino J, Crane LR, Daley L, Dandridge D, D'Antuono V, Darcourt Rizo Patron JG, DeHovitz JA, DeJesus E, DesJardin J, Diaz-Linares M, Dietrich C, Dodson P, Dolce E, Elliott K, Erickson D, Estes M, Faber LL, Falbo J, Farrough MJ, Farthing CF, Ferrell-Gonzalez P, Flynn H, Frank C, Frank M, Freeman KF, French N, Friedland G, Fujita N, Gahagan L, Genther K, Gilson I, Goetz MB, Goodwin E, Graziano F, Guity GK, Gulick P, Gunderson ER, Hale CM, Hannah K, Henderson H, Hennessey K, Henry WK, Higgins DT, Hodder SL, Horowitz HW, Howe-Pittman M, Hubbard J, Hudson R, Hunter H, Hutelmyer C, Insignares MT, Jackson L, Jenny L, John M, Johnson DL, Johnson G, Johnson J, Johnson L, Kaatz J, Kaczmarski J, Kagan S, Kantor C, Kempner T, Kieckhaus K, Kimmel N, Klaus BM, Klimas N, Koeppe JR, Koirala J, Kopka J, Kostmann JR, Kozal MJ, Kumar A, Labriola A, Lampiris H, Lamprecht C, Lattanzi KM, Lee J, Leggett J, Long C, Loquere A, Loveless K, Lucasti CJ, Luskin-Hawk R, MacVeigh M, Makohon LH, Mannheimer S, Markowitz NP, Marks C, Martinez N, Martorell C, McFeaters E, McGee B, McIntyre DM, McKee J, McManus E, Melecio LG, Melton D, Mercado S, Merrifield E, Mieras JA, Mogyoros M, Moran FM, Murphy K, Mushatt D, Mutic S, Nadeem I, Nahass R, Nixon D, O'Brien S, Ognjan A, O'Hearn M, O'Keefe K, Okhuysen PC, Oldfield E, Olson D, Orenstein R, Ortiz R, Osterberger J, Owen W, Parpart F, Pastore-Lange V, Paul S, Pavlatos A, Pearce DD, Pelz R, Perez G, Peterson S, Pierone G Jr, Pitrak D, Powers SL, Pujet HC, Raaum JW, Ravishankar J, Reeder J, Regevik N, Reilly NA, Reyelt C, Riddell J 4th, Rimland D, Robinson ML, Rodriguez AE, Rodriguez-Barradas MC, Rodriguez Derouen V, Roland R, Rosmarin C, Rossen WL, Rouff JR, Sampson JH, Sands M, Savini C, Schrader S, Schulte MM, Scott C, Scott R, Seedhom H, Sension M, Sheble-Hall A, Sheridan A, Shuter J, Slater LN, Slotten R, Slowinski D, Smith M, Snap S, Somboonwit C, States DM, Stewart M, Stringer G, Sullivan J, Summers KK, Swanson K, Sweeton IB, Szabo S, Tedaldi EM, Telzak EE, Temesgen Z, Thomas D, Thompson MA, Thompson S, Bong TH, Tobin C, Uy J, Vaccaro A, Vasco LM, Vecino I, Verlinghieri GK, Visnegarwala F, Wade BH, Watson V, Weis SE, Weise JA, Weissman S, Wilkin AM, Williams L, Witter JH, Wojtusic L, Wright TJ, Yeh V, Young B, Zeana C, Zeh J, Savio E, Vacarezza M.

Abstract

BACKGROUND:

Activation and coagulation biomarkers were measured within the Strategies for Management of Antiretroviral Therapy (SMART) trial. Their associations with opportunistic disease (OD) in human immunodeficiency virus (HIV)-positive patients were examined.

METHODS:

Inflammatory (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], amyloid-A, and amyloid-P) and coagulation (D-dimer and prothrombin-fragment 1+2) markers were determined. Conditional logistic regression analyses were used to assess associations between these biomarkers and risk of OD.

RESULTS:

The 91 patients who developed an OD were matched to 182 control subjects. Patients with an hsCRP level > or =5 microg/mL at baseline had a 3.5 higher odds of OD (95% confidence interval [CI], 1.5-8.1) than did those with an hsCRP level <1 microg/mL (P=.003, by test for trend) and patients with an IL-6 level > or =3 pg/mL at baseline had a 2.4 higher odds of OD (95% CI, 1.0-5.4) than did those with an IL-6 level <1.5 pg/mL (P=.02, by test for trend). No other baseline biomarkers predicted development of an OD. Latest follow-up hsCRP level for those with an hsCRP level > or =5 microg/mL (compared with a level <1 microg/mL; odds ratio [OR], 7.6; 95% CI, 2.0-28.5; [P=.002, by test for trend), latest amyloid-A level for those with an amyloid-A level > or =6 mg/L (compared with a level <2 mg/L; OR, 3.8; 95% CI, 1.1-13.4; P=.03, by test for trend), and latest IL-6 level for those with an IL-6 level > or =3 pg/mL (compared with a level <1.5 pg/mL; OR 2.4; 95% CI, 0.7-8.8; P=.04, by test for trend) were also associated with development of an OD.

CONCLUSIONS:

Higher IL-6 and hsCRP levels independently predicted development of OD. These biomarkers could provide additional prognostic information for predicting the risk of OD.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00027352 NCT00027352.

PMID:
19678756
PMCID:
PMC2892757
DOI:
10.1086/605447
[PubMed - indexed for MEDLINE]
Free PMC Article
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