Browsing by Author "Tierney, Camlin"

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    Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine
    (Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-09-01) Wyatt, Christina M.; Kitch, Douglas; Gupta, Samir K.; Tierney, Camlin; Daar, Eric S.; Sax, Paul E.; Ha, Belinda; Melbourne, Kathleen; McComsey, Grace A.; AIDS Clinical Trials Group Study A5224s Team; Department of Medicine, IU School of Medicine
    BACKGROUND: Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria. METHODS: We examined changes in urine protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART-naive participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121) with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz. RESULTS: At baseline, 18% of participants had clinically significant proteinuria (UPCR ≥200 mg/g), and 11% had clinically significant albuminuria (UACR ≥30 mg/g). The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups. In intention-to-treat analyses, there was a significant effect of NRTI component on fold change in UPCR (P = 0.011) and UACR (P = 0.018) from baseline to week 96, with greater improvements in participants randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on fold change in UPCR (P = 0.23) or UACR (P = 0.88), and no significant interactions between NRTI and NNRTI/PI components. CONCLUSIONS: In this prespecified secondary analysis, ART initiation was associated with improvements in proteinuria and albuminuria, with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC. These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens. Future studies should consider the long-term clinical significance of these findings.
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    Cystatin C-Based Renal Function Changes After Antiretroviral Initiation: A Substudy of a Randomized Trial
    (Oxford University Press, 2014-04-16) Gupta, Samir K.; Kitch, Douglas; Tierney, Camlin; Daar, Eric S.; Sax, Paul E.; Melbourne, Kathleen; Ha, Belinda; McComsey, Grace A.; Department of Medicine, IU School of Medicine
    Background.  The effects of antiretrovirals on cystatin C-based renal function estimates are unknown. Methods.  We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz. Results.  Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .016) and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; P = .030) and 2012 CKD-EPI cystatin C-creatinine (P = .025). Renal function changes significantly improved (or declined less) with efavirenz compared with atazanavir/ritonavir (P < .001 for all equations). Mean (95% confidence interval) renal function changes specifically for tenofovir/emtricitabine combined with atazanavir/ritonavir were −8.3 (−14.0, −2.6) mL/min with Cockcroft-Gault; −14.9 (−19.7, −10.1) mL/min per 1.732 with Modification of Diet in Renal Disease; −12.8 (−16.5, −9.0) mL/min per 1.732 with 2009 CKD-EPI; +8.9 (4.2, 13.7) mL/min per 1.732 with 2012 CKD-EPI cystatin C; and −1.2 (−5.1, 2.6) mL/min per 1.732 with 2012 CKD-EPI cystatin C-creatinine. Renal function changes for the other treatment arms were more favorable but similarly varied by estimating equation. Conclusions.  Antiretroviral-associated changes in renal function vary in magnitude and direction based on the estimating equation used.
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    Markers of renal disease and function are associated with systemic inflammation in HIV infection: Renal and inflammatory markers in HIV infection
    (Wiley Blackwell (Blackwell Publishing), 2015-11) Gupta, Samir K; Kitch, Douglas; Tierney, Camlin; Melbourne, Kathleen; Ha, Belinda; McComsey, Grace A; AIDS Clinical Trials Group Study A5224s Team; Department of Medicine, IU School of Medicine
    OBJECTIVES: Both renal disease and systemic inflammation predict non-AIDS-defining events and overall mortality in HIV-infected patients. Here, we sought to determine the relationships between renal disease and circulating inflammation markers. METHODS: We performed a secondary analysis of AIDS Clinical Trials Group Study A5224s to determine if markers of renal disease [urine protein:creatinine ratio (uPCR), urine albumin:creatinine ratio (uACR), and estimated glomerular filtration rate (eGFR), using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine and cystatin C-creatinine] were associated with markers of systemic inflammation [high-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor (TNF)-α, soluble TNF-α receptor I (sTNFRI), sTNFRII, and soluble vascular cellular and intercellular adhesion molecules]. We correlated these renal and inflammatory markers prior to antiretroviral initiation and after 96 weeks of therapy. RESULTS: We found that eGFR (estimated using CKD-EPI cystatin C-creatinine), uPCR, and uACR were significantly correlated with most assessed markers of systemic inflammation prior to antiretroviral initiation. uPCR and eGFR (using CKD-EPI cystatin C-creatinine), but not uACR, remained significantly correlated with most of the assessed inflammatory markers after 96 weeks of antiretroviral therapy (ART). Most of these correlations, although statistically significant, were < 0.50. eGFR using CKD-EPI creatinine was much less frequently associated with inflammation markers and only significantly correlated with sTNFR1 at week 0 and with sTNFRI and II at week 96. CONCLUSIONS: Renal disease and function were associated with systemic inflammation in HIV infection, both before and after ART. Systemic inflammation may partially explain the relationships between proteinuria, albuminuria, and reduced renal function and future adverse outcomes.