Association Between Antiretroviral Exposure and Renal Impairment Among HIV-Positive Persons With Normal Baseline Renal Function: the D:A:D Studya

Abstract

Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment in HIV-positive persons without preexisting renal impairment. Increased tenofovir discontinuation rates with decreasing eGFR may have prevented further deteriorations. After discontinuation, the ARV-associated incidence rates decreased.

Renal Impairment and Cardiovascular Disease in HIV-Positive Individuals: The D:A:D Study

“…Interestingly, these previous data also supported a strong association between CVD and renal function, which significantly diminished after accounting for other risk factors, suggesting an underlying biological mechanism at least partly mediated by other factors. We have also previously showed an association between the use of certain antiretroviral drugs and CVD and renal impairment [28,30,32]. The results of this analysis are entirely consistent with these prior findings, and adjustment for the use of individual antiretroviral drugs did not have any major impact on the association between impaired eGFR and CVD.…”

“…In previous studies from D:A:D, we investigated the inverse relation between CVD events and eGFR, focusing on CVD as a risk factor for various levels of chronic renal impairment [28,29,31]. Interestingly, these previous data also supported a strong association between CVD and renal function, which significantly diminished after accounting for other risk factors, suggesting an underlying biological mechanism at least partly mediated by other factors.…”

“…Persons with <3 months of follow-up from the first to the last eGFR measurement were excluded. The Cockcroft-Gault equation [25], standardized for body surface area [26], was used to estimate creatinine clearance, a surrogate for eGFR in this analysis [27,28]. As several cohorts participating in D:A:D are prohibited from collecting ethnicity information, the Cockcroft-Gault equation was used, rather than an equation including ethnicity.…”

Long-term comparative and prospective cohort study of renal function in patients with HIV infection treated with tenofovir disoproxil fumarate

“…Moreover, this bias could explain another significant limitation of our work, which is the higher prevalence of boosted protease inhibitor (PI) as part of the ART regimen in TDF group patients. Boosted PIs have been related to a higher incidence of kidney disease in many observational studies [10,22], although data from clinical trials suggest a reasonable renal safety profile [23]. In our study, the use of PIs did not show any significant relationship with CRDRF so its role as a potential confounder in our study might be limited.…”

“…Moreover, large clinical trials with long follow-up periods of more than 144 weeks in naïve patients have shown a renal safety profile of ART containing TDF, either similar to other ART without it, or with small significant declines in the estimated glomerular filtration rate (eGFR) of clinical implications difficult to ascertain [7][8][9]. Observational studies with longer follow-up periods suggest a more deleterious effect on the renal function, and point that TDF is associated with a higher incidence of chronic kidney disease [10][11][12][13][14][15][16][17]. Overall, these results have shown either a modest or absent decline in renal function associated with TDF use after short follow-up periods of months or very few years, while studies with longer follow-up periods suggest a more relevant decrease in renal function [13][14][15][16][17].…”