A Comparative Analysis of Risk Factors Associated With Renal Impairment and Highly Active Antiretroviral Therapy

Neesha Rockwood,Julia Sirokosta,Sundhiya Mandalia

doi:10.4172/jaa.1000041

Abstract

Background: The effect of boosted protease inhibitors (PI) on renal function is unclear. Methods: We assessed and compared the risk of developing renal impairment in individuals commencing 3 first line PI-based regimens vs a non-nucleoside reverse transcriptase inhibitor- based regimen. Patients commencing efavirenz, darunavir, atazanavir or lopinavir with 2 nucleos(t)ide reverse transcriptase inhibitors from June 2006 - February 2010, with baseline eGFR>60ml/min per 1.73m2 were included. Univariate and adjusted Cox’s proportional hazards regression models were used to examine likelihood of developing renal impairment (defined as eGFR< 60ml/min per 1.73m2). Results: 386 of 2115 treated individuals developed renal impairment over 2680 person years of follow up. By univariate analysis, female gender (HR 1.51, p 0.002), baseline age (p<0.001), baseline eGFR (p<0.001), darunavir (HR 1.53, p<0.001), atazanavir (HR 1.27, p 0.036), lopinavir (HR 1.71, p<0.001), prior tenofovir exposure (HR 1.68, p<0.001), prior indinavir exposure (HR 2.03, p<0.001) and total duration of tenofovir exposure (HR 1.09, p<0.001) were associated with an increased risk of renal impairment. By multivariate analysis, treatment with atazanavir (HR 1.52, p 0.004) and lopinavir (HR 1.61, p<0.017) but not darunavir (HR 1.31, p 0.108) were associated with an increased risk of renal impairment compared with efavirenz. Conclusion: There was a significantly increased risk of developing renal impairment associated with atazanavir and lopinavir independent of exposure to tenofovir.

Highlights

In the era of Highly Active Antiretroviral Therapy (HAART), there has been a reduction in mortality and morbidity associated with renal disease, including HIV-associated nephropathy, HIV-associated immune complex kidney disease and thrombotic microangiopathy [1,2]
Creatinine based estimates of glomerular filtration rate have not been validated in the HIV population, they have been widely used in clinical practice to measure renal function [8]
We aimed to assess the impact of the protease inhibitors (PI) on renal function having adjusted for past and total duration of TFV exposure

Summary

Introduction

In the era of Highly Active Antiretroviral Therapy (HAART), there has been a reduction in mortality and morbidity associated with renal disease, including HIV-associated nephropathy, HIV-associated immune complex kidney disease and thrombotic microangiopathy [1,2]. As those individuals infected with HIV achieve a longer survival, the burden of chronic kidney disease (CKD) is increasing. This is in the context of increased traditional risk factors for CKD including cardiovascular disease, hypertension and diabetes mellitus [3]. The effect of boosted protease inhibitors (PI) on renal function is unclear

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