Increased Time Exposure to Tenofovir Is Associated with a Greater Decrease in Estimated Glomerular Filtration Rate in HIV Patients with Kidney Function of Less than 60 ml/min/1.73 m²

Abstract

Tenofovir (TDF), atazanovir (ATAZ) and indinavir (IND) have been reported as possible risk factors for incident chronic kidney disease (CKD) in HIV-infected patients. We investigated the relationship between the duration of antiretroviral exposure and estimated glomerular filtration rate (eGFR) evolution in CKD patients. In a cohort of 1,750 HIV-infected patients, we identified 121 CKD patients with a mean follow-up of 44 ± 35 months. The relationship between mean eGFR at baseline, eGFR slope and time exposure to antiretroviral treatment as well as confounding factors were investigated using a joint modeling procedure. Seventy (58%), 30 (25%) and 33 patients (27%), with a mean age of 50.3 ± 11.7 years, mean eGFR at baseline of 53.0 ± 0.8 (ml/min/1.73 m²) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m²/year, were exposed to TDF, ATAZ and IND, respectively. In univariate analysis, hepatitis C virus infection, decreased nadir of log CD4 count, high blood pressure at baseline, angiotensin-converting enzyme inhibitor treatment and greater time exposure to TDF during follow-up were associated with a higher slope, whereas greater time exposure to IND was associated with a lower slope. In multivariate analysis, higher TDF time exposure was still significantly associated with eGFR decline, with a dose-effect relationship (slope ± standard error of the mean: 1.1 ± 0.1, 0.5 ± 0.1, –0.07 ± 0.08 and –0.87 ± 0.06 ml/min/1.73 m²/year for no time exposure, <34, 34–67 and ≥67%, respectively; trend test: p < 0.001), whereas the IND time exposure association was abolished. In HIV patients with CKD, a greater TDF time exposure was independently associated, in a graded manner, with a greater eGFR decline.

Tenofovir monotherapy for hepatitis B after 1 year does not produce renal dysfunction, but is associated with hyperparathyroidism not related to vitamin D

“…Interactions among some carriers can alter the overall traffic flow of the drug, favoring intracellular accumulation and toxicity [22]. The use of TDF has been associated with an increased risk for the development of acute or chronic kidney injury and also with different forms of renal toxicity in HIV patients [23][24][25]. From HIV patient data, some reports have associated renal toxicity with a range of variables such as the duration of drug exposure, drug combinations, age, ethnicity, and body mass [26,27].…”

Incidence and risk factors for tenofovir-associated renal toxicity in HIV-infected patients

“…Moreover, Fafin et al investigated the association between the duration of treatment with certain antiretroviral drugs (TDF, atazanavir and indinavir) and the evolution of eGFR in HIV-infected patients. Among a cohort of 1750 patients, the average time to chronic kidney disease was 44 months, linking increased TDF treatment duration and dose with a reduction in eGFR [41]. In addition, another trial, in which baseline SCr levels were measured at one, three and 12 months after treatment initiation, a dose-time dependent association between treatment with TDF and a decrease in eGFR was suggested [42].…”

Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens

“…Tenofovir is primarily eliminated via the kidney by a combination of glomerular filtration and active tubular secretion [4]. Systematic reviews and meta-analyses of randomized controlled trials have indicated an association between TDF-based regimens and an increased risk of renal impairment and bone demineralization [5,6,7], with longer-term studies suggesting that this risk is further increased with cumulative exposure to tenofovir [8,9,10,11]. …”