9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 19-21 July 2007, Sydney, Australia

PROTEINURIA, CREATININE CLEARANCE AND IMMUNE ACTIVATION IN HIV-INFECTED SUBJECTS: A SECONDARY ANALYSIS OF TREATMENT-NAÏVE STUDIES ACTG 384, A5095 AND A5001

Antiviral Therapy 2007; 12(Suppl. 2):L17 (abstract no. O-21)

SK Gupta¹, L Komarow², RM Gulick³, RB Pollard⁴, GK Robbins⁵, N Franceschini⁶, LA Szczech⁷, SL Koletar⁸ and RC Kalayjian^9
1Indiana University School of Medicine, Indianapolis, IN, USA; ²SDAC/Harvard School of Public Health, Boston, MA, USA; ³Weill Medical College of Cornell University, NY, NY, USA; ⁴University of California, Davis Medical Center, Sacramento, CA, USA; ⁵Harvard University, Boston, MA, USA; ⁶University of North Carolina, Chapel Hill, NC, USA; ⁷Duke University Medical Center, Durham, NC, USA; ⁸The Ohio State University, Columbus, OH, USA; ⁹MetroHealth Clinical Research, Cleveland, OH, USA

AIM: Proteinuria and increased serum creatinine, independently of viral load and CD4 count, predict progression to AIDS and overall mortality in HIV-infected women, although an explanation for these relationships remains unclear. Because activated T cells are more commonly found in the kidneys of HIV-infected patients with poorer renal function, we hypothesized that proteinuria and decreased creatinine clearance (CrCl) may be markers of higher peripheral immune activation, which itself is a strong predictor of outcomes.

METHODS: Treatment-naïve subjects enrolled in ACTG therapeutic studies 384 and A5095 with renal and advanced flow cytometry data at baseline (advanced flow data for the A5095 subjects were provided by the longitudinal follow-up study A5001) were included in the analysis. Levels of immune activation, defined as the percentage of peripheral blood activated CD8 lymphocytes (CD8+/CD38+/HLA-DR+ cells), were compared between those with and without dipstick proteinuria ≥1+ and between those with and without CrCl <90 ml/min (estimated using the Cockcroft–Gault equation). Comparisons between groups were performed using the Wilcoxon Rank Sum test stratified by study cohort.

RESULTS: Dipstick proteinuria, CrCl <90 ml/min, and CrCl <60 ml/min were present, respectively, in 73/1,012 (7%), 195/1,071 (18%), and 9/1,071 (1%) of the subjects at baseline. Proteinuria was significantly associated with a higher median percentage of activated CD8 cells compared with those without proteinuria in the total cohort (55% versus 50%; P=0.01); significant associations were also found in the black non-Hispanic (n=346), Hispanic (n=176), and male subgroups (n=846), but not in the white non-Hispanic or female subgroups. Importantly, these differences were primarily driven by the ACTG 384 cohort (n=576/1,012). Percentages of activated CD8 cells were not significantly different between those with CrCl <90 ml/min compared with higher CrCl (53% versus 49%; P=0.08) in the total cohort, but the differences were significant (53% versus 48%; P=0.04) in the ACTG 384 cohort (n=615/1,071).

CONCLUSIONS: Dipstick proteinuria, but not CrCl, was associated with greater levels of activated peripheral CD8 cells in this study of ART-naïve patients with relatively preserved glomerular function. The presence of dipstick proteinuria may be an inexpensive and easily obtained identifier of HIV-infected patients with higher immune activation and consequently greater risk for poor outcomes.

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2007-07-24
O-21

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