Interruption of antiretroviral therapy is associated with increased plasma cystatin C.
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).


CONCLUSIONS
These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.
Mocroft
Amanda
A
University College London Medical School, London, UK. a.mocroft@pcps.ucl.ac.uk
Wyatt
Christina
C
Szczech
Lynda
L
Neuhaus
Jacquie
J
El-Sadr
Wafaa
W
Tracy
Russell
R
Kuller
Lewis
L
Shlipak
Michael
M
Angus
Brian
B
Klinker
Harting
H
Ross
Michael
M
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D055316:Cystatin C / Q000097:blood*; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D019562:Viral Load
D019380:Anti-HIV Agents; D015415:Biomarkers; D055316:Cystatin C; D008055:Lipids