Document Detail


Platelet count kinetics following interruption of antiretroviral treatment.
MedLine Citation:
PMID:  23018440     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART.
DESIGN: SMART patients from sites that determined platelets routinely.
METHODS: Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2.
RESULTS: Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: -24 000/μl (-54 000 to 4000) vs. 3000 (-22 000 to 24 000), respectively, P < 0.0001)] and the rate of developing thrombocytopenia (<100 000/μl) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2-2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = -0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels.
CONCLUSION: Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study.
Authors:
Eva Zetterberg; Jacqueline Neuhaus; Jason V Baker; Charurut Somboonwit; Josep M Llibre; Adrian Palfreeman; Maria Chini; Jens D Lundgren;
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  AIDS (London, England)     Volume:  27     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-12     Completed Date:  2013-06-17     Revised Date:  2014-05-21    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  59-68     Citation Subset:  IM; X    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00027352
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-HIV Agents / administration & dosage*,  blood
Antifibrinolytic Agents / administration & dosage*
Biological Markers / blood
Blood Coagulation / drug effects
CD4 Lymphocyte Count
Drug Administration Schedule
Female
Fibrin Fibrinogen Degradation Products / administration & dosage*
Follow-Up Studies
HIV Seropositivity / blood*,  drug therapy
Humans
Inflammation / blood
Male
Middle Aged
Platelet Count*
Proportional Hazards Models
Retrospective Studies
Treatment Outcome
Viral Load
Virus Replication / drug effects*
Grant Support
ID/Acronym/Agency:
MC_U122886352//Medical Research Council; U01 AI068641/AI/NIAID NIH HHS; U01-AI042170/AI/NIAID NIH HHS; U01-AI046362/AI/NIAID NIH HHS; U01-AI068641/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Antifibrinolytic Agents; 0/Biological Markers; 0/Fibrin Fibrinogen Degradation Products; 0/fibrin fragment D
Investigator
Investigator/Affiliation:
J D Lundgren / ; K B Jensen / ; D C Gey / ; L Borup / ; M Pearson / ; P O Jansson / ; B G Jensen / ; J Tverland / ; H Juncker-Benzon / ; Z Fox / ; A N Phillips / ; J H Darbyshire / ; A G Babiker / ; A J Palfreeman / ; S L Fleck / ; W Dodds / ; E King / ; B Cordwell / ; F van Hooff / ; Y Collaco-Moraes / ; D A Cooper / ; S Emery / ; F M Drummond / ; S A Connor / ; C S Satchell / ; S Gunn / ; S Oka / ; M A Delfino / ; K Merlin / ; C McGinley / ; F Gordin / ; E Finley / ; D Dietz / ; C Chesson / ; M Vjecha / ; B Standridge / ; J D Neaton / ; G Bartsch / ; A DuChene / ; M George / ; B Grund / ; M Harrison / ; E Krum / ; G Larson / ; C Miller / ; R Nelson / ; J Neuhaus / ; M P Roediger / ; T Schultz / ; R Prineas / ; C Campbell / ; Z -M Zhang / ; G Perez / ; A Lifson / ; D Duprez / ; J Hoy / ; C Lahart / ; D Perlman / ; R Price / ; R Prineas / ; F Rhame / ; J Sampson / ; J Worley / ; M Rein / ; R DerSimonian / ; E S Daar / ; N N Dubler / ; T R Fleming / ; D J Freeman / ; J P Kahn / ; K M Kim / ; G Medoff / ; J F Modlin / ; R Moellering / ; B E Murray / ; B Pick / ; M L Robb / ; D O Scharfstein / ; J Sugarman / ; A Tsiatis / ; C Tuazon / ; L Zoloth / ; K Klingman / ; S Lehrman / ; J Lazovski / ; W H Belloso / ; M H Losso / ; J A Benetucci / ; S Aquilia / ; V Bittar / ; E P Bogdanowicz / ; P E Cahn / ; A D Casiró / ; I Cassetti / ; J M Contarelli / ; J A Corral / ; A Crinejo / ; L Daciuk / ; D O David / ; G Guaragna / ; M T Ishida / ; A Krolewiecki / ; H E Laplume / ; M B Lasala / ; L Lourtau / ; S H Lupo / ; A Maranzana / ; F Masciottra / ; M Michaan / ; L Ruggieri / ; E Salazar / ; M Sánchez / ; C Somenzini / ; J F Hoy / ; G D Rogers / ; A M Allworth / ; J St C Anderson / ; J Armishaw / ; K Barnes / ; A Carr / ; A Chiam / ; J C P Chuah / ; M C Curry / ; R L Dever / ; W A Donohue / ; N C Doong / ; D E Dwyer / ; J Dyer / ; B Eu / ; V W Ferguson / ; M A H French / ; R J Garsia / ; J Gold / ; J H Hudson / ; S Jeganathan / ; P Konecny / ; J Leung / ; C L McCormack / ; M McMurchie / ; N Medland / ; R J Moore / ; M B Moussa / ; D Orth / ; M Piper / ; T Read / ; J J Roney / ; N Roth / ; D R Shaw / ; J Silvers / ; D J Smith / ; A C Street / ; R J Vale / ; N A Wendt / ; H Wood / ; D W Youds / ; J Zillman / ; A Rieger / ; V Tozeau / ; A Aichelburg / ; N Vetter / ; N Clumeck / ; S Dewit / ; A de Roo / ; K Kabeya / ; P Leonard / ; L Lynen / ; M Moutschen / ; E O'Doherty / ; L C Pereira / ; T N L Souza / ; M Schechter / ; R Zajdenverg / ; M M T B Almeida / ; F Araujo / ; F Bahia / ; C Brites / ; M M Caseiro / ; J Casseb / ; A Etzel / ; G G Falco / ; E C J Filho / ; S R Flint / ; C R Gonzales / ; J V R Madruga / ; L N Passos / ; T Reuter / ; L C Sidi / ; A L C Toscano / ; D Zarowny / ; E Cherban / ; J Cohen / ; B Conway / ; C Dufour / ; M Ellis / ; A Foster / ; D Haase / ; H Haldane / ; M Houde / ; C Kato / ; M Klein / ; B Lessard / ; A Martel / ; C Martel / ; N McFarland / ; E Paradis / ; A Piche / ; R Sandre / ; W Schlech / ; S Schmidt / ; F Smaill / ; B Thompson / ; S Trottier / ; S Vezina / ; S Walmsley / ; M J Wolff Reyes / ; R Northland / ; L Ostergaard / ; C Pedersen / ; H Nielsen / ; L Hergens / ; I R Loftheim / ; K B Jensen / ; M Raukas / ; K Zilmer / ; J Justinen / ; M Ristola / ; P M Girard / ; R Landman / ; S Abel / ; S Abgrall / ; K Amat / ; L Auperin / ; R Barruet / ; A Benalycherif / ; N Benammar / ; M Bensalem / ; M Bentata / ; J M Besnier / ; M Blanc / ; O Bouchaud / ; A Cabié / ; P Chavannet / ; J M Chennebault / ; S Dargere / ; X de la Tribonniere / ; T Debord / ; N Decaux / ; J Delgado / ; M Dupon / ; J Durant / ; V Frixon-Marin / ; C Genet / ; L Gérard / ; J Gilquin / ; B Hoen / ; V Jeantils / ; H Kouadio / ; P Leclercq / ; J -D Lelièvre / ; Y Levy / ; C P Michon / ; P Nau / ; J Pacanowski / ; C Piketty / ; I Poizot-Martin / ; I Raymond / ; D Salmon / ; J L Schmit / ; M A Serini / ; A Simon / ; S Tassi / ; F Touam / ; R Verdon / ; P Weinbreck / ; L Weiss / ; Y Yazdanpanah / ; P Yeni / ; G Fätkenheuer / ; S Staszewski / ; F Bergmann / ; S Bitsch / ; J R Bogner / ; N Brockmeyer / ; S Esser / ; F D Goebel / ; M Hartmann / ; H Klinker / ; C Lehmann / ; T Lennemann / ; A Plettenberg / ; A Potthof / ; J Rockstroh / ; B Ross / ; A Stoehr / ; J C Wasmuth / ; K Wiedemeyer / ; R Winzer / ; A Hatzakis / ; G Touloumi / ; A Antoniadou / ; G L Daikos / ; A Dimitrakaki / ; P Gargalianos-Kakolyris / ; M Giannaris / ; A Karafoulidou / ; A Katsambas / ; O Katsarou / ; A N Kontos / ; T Kordossis / ; M K Lazanas / ; P Panagopoulos / ; G Panos / ; V Paparizos / ; V Papastamopoulos / ; G Petrikkos / ; H Sambatakou / ; A Skoutelis / ; N Tsogas / ; G Xylomenos /
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