Abstract
ObjectiveWe investigated whether patients receiving selected antiretroviral combinations had a higher risk of chronic kidney disease (CKD) using traditional regression modeling and a causal approach in a large prospective cohort.Patients and methodsFor the purpose of this study, we selected 6301 patients who (i) started their first antiretroviral regimen after 1st January 2004, (ii) had at least one serum creatinine measurement within 6 months before ART initiation (study entry), and (iii) had at least two measurements after study entry. Baseline eGFR was defined from the last serum creatinine measurement before study entry. All eGFR values were calculated using the Modification of Diet and Renal Disease (MDRD) equation. Both traditional Cox proportional hazards model and Cox marginal structural models were applied. Distinct coding for antiretroviral therapy exposure were investigated as well as double robust estimators.ResultsOverall we showed that patients receiving tenofovir (TDF) with a ritonavir boosted protease inhibitor (rbPI) exhibited a higher risk of CKD compared with patients who received TDF with a non-nucleosidic reverse transcriptase inhibitor (NNRTI). Such an increased risk was observed considering both initial and current regimens. Our analysis revealed a clinician-driven switch away from TDF among persons experiencing a decline in renal function while receiving this drug.ConclusionOur results show that combination of TDF and boosted protease inhibitor is associated with a higher CKD risk than TDF and a NNRTI.
Highlights
Patients living with HIV have an increased risk of chronic kidney disease (CKD) by comparison with the general age-matched population, for various reasons including the use of some antiretroviral agents (ARVs) [1, 2]
Overall we showed that patients receiving tenofovir (TDF) with a ritonavir boosted protease inhibitor exhibited a higher risk of CKD compared with patients who received TDF with
Our results show that combination of TDF and boosted protease inhibitor is associated with a higher CKD risk than TDF and a nucleosidic reverse transcriptase inhibitor (NNRTI)
Summary
Patients living with HIV have an increased risk of chronic kidney disease (CKD) by comparison with the general age-matched population, for various reasons including the use of some antiretroviral agents (ARVs) [1, 2]. Many studies aimed to investigate CKD risk factors, including both traditional renal risk factors and ARVs. Summarizing the information is complex due to the various studied populations, endpoints, statistical methods and variables coding. Different statistical methods were used to investigate the association between ART exposure and occurrence of CKD, with differences in the assessment of the association between CKD and ART exposure, including different coding of ART exposure (current use versus past use, cumulative exposure) [7, 9]. Some authors have only considered the CKD risk in relation with the initial ARV regimen [10], whether or not patients remained on this regimen, whereas others investigated current/past ARV exposure or cumulative exposure [5,6,7, 11]. Analyses using marginal structural models (MSM) censored patients upon any change of ARV, ensuring an appropriate adjustment for confounding factors but limiting the number of events to those occurring while patients received their original ARV regimen [10, 12]
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