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.
aCopenhagen University Hospital/Rigshospitalet and University of Copenhagen, Denmark
bSkane University Hospital, Malmö, Sweden
cUniversity of Minnesota
dHennepin County Medical Center, Minneapolis, Minnesota
eUniversity of South Florida, Tampa, Florida, USA
fLluita contra la SIDA Foundation, University Hospital Germans Trias i Pujol (Badalona), Universitat Autònoma de Barcelona, Spain
gDepartment GU Medicine, University Hospitals Leicester, UK
hRed Cross General Hospital, Athens, Greece.
*Authors Eva Zetterberg and Jacqueline Neuhaus contributed equally.
Correspondence to Dr Jens D. Lundgren, Copenhagen University Hospital/Rigshospitalet and University of Copenhagen, Copenhagen HIV Programme (21.1), Panum Institute, Blegdamvej 3B, 2200 Copenhagen N, Denmark. E-mail: email@example.com
Received 7 June, 2012
Revised 30 August, 2012
Accepted 4 September, 2012
Clinical Trials.gov identifier: NCT00027352.