Interruption of antiretroviral therapy is associated with increased plasma cystatin C

Amanda Mocroft; Christina Wyatt; Lynda Szczech; Jacquie Neuhaus; Wafaa El-Sadr; Russell Tracy; Lewis Kuller; Michael Shlipak; Brian Angus; Harting Klinker; Michael Ross; Jens Lundgren; INSIGHT SMART Study Group

doi:10.1097/QAD.0b013e32831cc129

Interruption of antiretroviral therapy is associated with increased plasma cystatin C

Amanda Mocroft, Christina Wyatt, Lynda Szczech, Jacquie Neuhaus, Wafaa El-Sadr, Russell Tracy, Lewis Kuller, Michael Shlipak, Brian Angus, Harting Klinker, Michael Ross, Jens Lundgren, INSIGHT SMART Study Group

Department of Immunology and Microbiology

46 Citations (Scopus)

Abstract

BACKGROUND: Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. METHODS: Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics. RESULTS: At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P = 0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023). CONCLUSION: These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.

Original language	English
Journal	AIDS
Volume	23
Issue number	1
Pages (from-to)	71-82
Number of pages	12
ISSN	0269-9370
DOIs	https://doi.org/10.1097/QAD.0b013e32831cc129
Publication status	Published - 2009

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@article{d96836f07eaa11df928f000ea68e967b,

title = "Interruption of antiretroviral therapy is associated with increased plasma cystatin C",

abstract = "BACKGROUND: Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. METHODS: Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics. RESULTS: At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P = 0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023). CONCLUSION: These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.",

author = "Amanda Mocroft and Christina Wyatt and Lynda Szczech and Jacquie Neuhaus and Wafaa El-Sadr and Russell Tracy and Lewis Kuller and Michael Shlipak and Brian Angus and Harting Klinker and Michael Ross and Jens Lundgren and {INSIGHT SMART Study Group}",

note = "Keywords: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Biological Markers; CD4 Lymphocyte Count; Cystatin C; Drug Administration Schedule; Female; Glomerular Filtration Rate; HIV Infections; Humans; Kidney; Lipids; Male; Middle Aged; Viral Load",

year = "2009",

doi = "10.1097/QAD.0b013e32831cc129",

language = "English",

volume = "23",

pages = "71--82",

journal = "AIDS, Supplement",

issn = "1350-2840",

publisher = "Lippincott Williams & Wilkins",

number = "1",

}

TY - JOUR

T1 - Interruption of antiretroviral therapy is associated with increased plasma cystatin C

AU - Mocroft, Amanda

AU - Wyatt, Christina

AU - Szczech, Lynda

AU - Neuhaus, Jacquie

AU - El-Sadr, Wafaa

AU - Tracy, Russell

AU - Kuller, Lewis

AU - Shlipak, Michael

AU - Angus, Brian

AU - Klinker, Harting

AU - Ross, Michael

AU - Lundgren, Jens

AU - INSIGHT SMART Study Group

N1 - Keywords: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Biological Markers; CD4 Lymphocyte Count; Cystatin C; Drug Administration Schedule; Female; Glomerular Filtration Rate; HIV Infections; Humans; Kidney; Lipids; Male; Middle Aged; Viral Load

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. METHODS: Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics. RESULTS: At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P = 0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023). CONCLUSION: These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.

AB - BACKGROUND: Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. METHODS: Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics. RESULTS: At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P = 0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023). CONCLUSION: These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.

U2 - 10.1097/QAD.0b013e32831cc129

DO - 10.1097/QAD.0b013e32831cc129

M3 - Journal article

C2 - 19050388

SN - 1350-2840

VL - 23

SP - 71

EP - 82

JO - AIDS, Supplement

JF - AIDS, Supplement

IS - 1

ER -

Interruption of antiretroviral therapy is associated with increased plasma cystatin C

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