TY - JOUR
T1 - Platelet count kinetics following interruption of antiretroviral treatment
AU - Zetterberg, Eva
AU - Nordwall, Jacqueline A
AU - Baker, Jason V.
AU - Somboonwit, Charurut
AU - Llibre, Josep M.
AU - Palfreeman, Adrian
AU - Chini, Maria
AU - Lundgren, Jens D.
PY - 2013/1/2
Y1 - 2013/1/2
N2 - 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. Design: 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:-24000/μl (-54000 to 4000) vs. 3000 (-22000 to 24000), respectively, P<0.0001)] and the rate of developing thrombocytopenia (<100000/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.
AB - 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. Design: 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:-24000/μl (-54000 to 4000) vs. 3000 (-22000 to 24000), respectively, P<0.0001)] and the rate of developing thrombocytopenia (<100000/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.
KW - D-dimer
KW - HIV
KW - antiretroviral therapy
KW - platelets
KW - strategies for management of antiretroviral therapy
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U2 - 10.1097/QAD.0b013e32835a104d
DO - 10.1097/QAD.0b013e32835a104d
M3 - Article
C2 - 23018440
AN - SCOPUS:84871610944
SN - 0269-9370
VL - 27
SP - 59
EP - 68
JO - AIDS
JF - AIDS
IS - 1
ER -