| Contributors: |
Ryom, L; Mocroft, A; Kirk, O; Worm, Sw; Kamara, Da; Reiss, P; Ross, M; Fux, Ca; Morlat, P; Moranne, O; Smith, C; Lundgren, Jd; D:A:D Study, Group; Dabis, F; El Sadr, W; Pradier, C; Weber, R; Law, M; Morfeldt, L; de Wit, S; Calvo, G; d'Arminio Monforte, A; Shortman, N; Butcher, D; Rode, R; Franquet, X; Powderly, W; Sabin, C; Phillips, A; Lundgren, J; Kamara, D; Tverland, J; Nielsen, J; Salbøl Brandt, R; Rickenbach, M; Fanti, I; Krum, E; Hillebregt, M; Geffard, S; Sundström, A; Delforge, M; Fontas, E; Torres, F; Mcmanus, H; Wright, S; Kjær, J; Sjøl, A; Meidahl, P; Helweg Larsen, J; Schmidt Iversen, J; Worm, S; Fux, C; de Wolf, F; Zaheri, S; Gras, L; Prins, Jm; Kuijpers, Tw; Scherpbier, Hj; Boer, K; van der Meer, Jt; Wit, Fw; Godfried, Mh; van der Poll, T; Nellen, Fj; Lange, Jm; Geerlings, Se; van Vugt, M; Vrouenraets, Sm; Pajkrt, D; van der Valk, M; Schreij, G |
| Description: |
BACKGROUND: Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown. METHODS: D:A:D study participants with an estimated glomerular filtration rate (eGFR) of ≥ 90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ≤ 70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ≤ 60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD]) or until the last eGFR measurement during follow-up. An eGFR was considered confirmed if it was detected at 2 consecutive measurements ≥ 3 months apart. Predictors and eGFR-related ARV discontinuations were identified using Poisson regression. RESULTS: Of 22 603 persons, 468 (2.1%) experienced a confirmed eGFR of ≤ 70 mL/min (incidence rate, 4.78 cases/1000 person-years of follow-up [95% confidence interval {CI}, 4.35-5.22]) and 131 (0.6%) experienced CKD (incidence rate, 1.33 cases/1000 person-years of follow-up [95% CI, 1.10-1.56]) during a median follow-up duration of 4.5 years (interquartile range [IQR], 2.7-6.1 years). A current eGFR of 60-70 mL/min caused significantly higher rates of discontinuation of tenofovir (adjusted incidence rate ratio [aIRR], 1.72 [95% CI, 1.38-2.14]) but not other ARVs compared with a current eGFR of ≥ 90 mL/min. Cumulative tenofovir use (aIRR, 1.18/year [95% CI, 1.12-1.25]) and ritonavir-boosted atazanavir use (aIRR, 1.19/year [95% CI, 1.09-1.32]) were independent predictors of a confirmed eGFR of ≤ 70 but were not significant predictors of CKD whereas ritonavir-boosted lopinavir use was a significant predictor for both end points (aIRR, 1.11/year [95% CI, 1.05-1.17] and 1.22/year [95% CI, 1.16-1.28], respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs. CONCLUSIONS: Tenofovir, ritonavir-boosted atazanavir, and ... |