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AIDS. 2013 Jan 2;27(1):59-68. doi: 10.1097/QAD.0b013e32835a104d.

Platelet count kinetics following interruption of antiretroviral treatment.

Collaborators (319)

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 CS, 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 Z-, 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, 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 PE, Casiró AD, Cassetti I, Contarelli JM, Corral JA, Crinejo A, Daciuk L, David DO, 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 S, 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 J-, 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 T, Plettenberg A, Potthof A, Rockstroh J, 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.

Author information

  • 1Copenhagen University Hospital/Rigshospitalet and University of Copenhagen, Denmark.

Abstract

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.

PMID:
23018440
[PubMed - indexed for MEDLINE]
PMCID:
PMC4024440
Free PMC Article

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