Platelet count kinetics following Interruption of antiretroviral treatment: Results from the SMART study.
(2013) In AIDS 27(1). p.59-68- Abstract
- OBJECTIVES:
To investigate the mechanisms of platelet kinetics in the SMART study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) (drug conservation [DC]) compared to continuous treatment (viral suppression [VS]). 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... (More) - OBJECTIVES:
To investigate the mechanisms of platelet kinetics in the SMART study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) (drug conservation [DC]) compared to continuous treatment (viral suppression [VS]). 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 DC group following randomization, but remained stable in the VS group [median (IQR) decline from study entry to month 4: -24,000/μL(-54,000-4,000) vs. 3000 (-22,000-24,000), respectively, p < 0.0001)] and the rate of developing thrombocytopenia (<100,000/μL) was significantly higher in the DC versus the VS arm (unadjusted DC/VS HR (95%CI) = 1.8 (1.2-2.7)). The decline in platelet count among DC participants on fully suppressive ART correlated with the rise in D-dimer from baseline to either month 1 or 2 (r = -0.41; p = 0.02). Among DC participants who resumed ART 74% recovered to their study entry platelet levels.
CONCLUSION:
Interrupting ART increases the risk of thrombocytopenia, but re-initiation 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 pro-coagulant activity requires further study. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3123566
- author
- Zetterberg, Eva LU ; Neuhaus, Jacqueline ; Baker, Jason V ; Somboonwit, Charurut ; Llibre, Josep M ; Palfreeman, Adrian ; Chini, Maria and Lundgren, Jens D
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- HIV, management of antiretroviral therapy, platelets, strategies for, D-dimer, antiretroviral therapy
- in
- AIDS
- volume
- 27
- issue
- 1
- pages
- 59 - 68
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000312358000008
- pmid:23018440
- scopus:84871610944
- pmid:23018440
- ISSN
- 1473-5571
- DOI
- 10.1097/QAD.0b013e32835a104d
- language
- English
- LU publication?
- yes
- id
- 46898a9c-5e0c-418d-a25c-c75f5ee44123 (old id 3123566)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23018440?dopt=Abstract
- date added to LUP
- 2016-04-01 10:47:15
- date last changed
- 2022-04-12 17:28:51
@article{46898a9c-5e0c-418d-a25c-c75f5ee44123,
abstract = {{OBJECTIVES:<br/><br>
To investigate the mechanisms of platelet kinetics in the SMART study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) (drug conservation [DC]) compared to continuous treatment (viral suppression [VS]). Follow up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. <br/><br>
<br/><br>
DESIGN:<br/><br>
SMART patients from sites that determined platelets routinely. <br/><br>
<br/><br>
METHODS:<br/><br>
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 DC group following randomization, but remained stable in the VS group [median (IQR) decline from study entry to month 4: -24,000/μL(-54,000-4,000) vs. 3000 (-22,000-24,000), respectively, p < 0.0001)] and the rate of developing thrombocytopenia (<100,000/μL) was significantly higher in the DC versus the VS arm (unadjusted DC/VS HR (95%CI) = 1.8 (1.2-2.7)). The decline in platelet count among DC participants on fully suppressive ART correlated with the rise in D-dimer from baseline to either month 1 or 2 (r = -0.41; p = 0.02). Among DC participants who resumed ART 74% recovered to their study entry platelet levels. <br/><br>
<br/><br>
CONCLUSION:<br/><br>
Interrupting ART increases the risk of thrombocytopenia, but re-initiation 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 pro-coagulant activity requires further study.}},
author = {{Zetterberg, Eva and Neuhaus, Jacqueline and Baker, Jason V and Somboonwit, Charurut and Llibre, Josep M and Palfreeman, Adrian and Chini, Maria and Lundgren, Jens D}},
issn = {{1473-5571}},
keywords = {{HIV; management of antiretroviral therapy; platelets; strategies for; D-dimer; antiretroviral therapy}},
language = {{eng}},
number = {{1}},
pages = {{59--68}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{AIDS}},
title = {{Platelet count kinetics following Interruption of antiretroviral treatment: Results from the SMART study.}},
url = {{http://dx.doi.org/10.1097/QAD.0b013e32835a104d}},
doi = {{10.1097/QAD.0b013e32835a104d}},
volume = {{27}},
year = {{2013}},
}