Platelet count kinetics following interruption of antiretroviral treatment

TY - JOUR

T1 - Platelet count kinetics following interruption of antiretroviral treatment

AU - Zetterberg, Eva

AU - Neuhaus, Jacqueline

AU - Baker, Jason V

AU - Somboonwit, Charurut

AU - Llibre, Josep M

AU - Palfreeman, Adrian

AU - Chini, Maria

AU - Lundgren, Jens D

AU - INSIGHT SMART Study Group

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 - Adult

KW - Anti-HIV Agents

KW - Antifibrinolytic Agents

KW - Biological Markers

KW - Blood Coagulation

KW - CD4 Lymphocyte Count

KW - Drug Administration Schedule

KW - Female

KW - Fibrin Fibrinogen Degradation Products

KW - Follow-Up Studies

KW - HIV Seropositivity

KW - Humans

KW - Inflammation

KW - Male

KW - Middle Aged

KW - Platelet Count

KW - Proportional Hazards Models

KW - Retrospective Studies

KW - Treatment Outcome

KW - Viral Load

KW - Virus Replication

U2 - 10.1097/QAD.0b013e32835a104d

DO - 10.1097/QAD.0b013e32835a104d

M3 - Journal article

C2 - 23018440

SN - 1350-2840

VL - 27

SP - 59

EP - 68

JO - AIDS, Supplement

JF - AIDS, Supplement

IS - 1

ER -