title: 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 m(2)) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m(2)/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 m(2)/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.
authors.affiliation: Department of Nephrology, Nice Hospital, University of Nice Sophia-Antipolis, Nice, France.
authors.forename: C
authors.initials: C
authors.lastname: Fafin
authors.forename: P
authors.initials: P
authors.lastname: Pugliese
authors.forename: J
authors.initials: J
authors.lastname: Durant
authors.forename: V
authors.initials: V
authors.lastname: Mondain
authors.forename: V
authors.initials: V
authors.lastname: Rahelinirina
authors.forename: F
authors.initials: F
authors.lastname: De Salvador
authors.forename: C
authors.initials: C
authors.lastname: Ceppi
authors.forename: I
authors.initials: I
authors.lastname: Perbost
authors.forename: E
authors.initials: E
authors.lastname: Rosenthal
authors.forename: P M
authors.initials: PM
authors.lastname: Roger
authors.forename: E
authors.initials: E
authors.lastname: Cua
authors.forename: P
authors.initials: P
authors.lastname: Dellamonica
authors.forename: V
authors.initials: V
authors.lastname: Esnault
authors.forename: C
authors.initials: C
authors.lastname: Pradier
authors.forename: O
authors.initials: O
authors.lastname: Moranne
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D012307:Risk Factors; D000068698:Tenofovir; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine