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

BACKGROUND: Since the beginning of highly active antiretroviral therapy utilization, the association of renal impairment with treatment toxicity is more prevalent. Tenofovir disoproxil fumarate (TDF) side effects include renal toxicity.

OBJECTIVE: To assess the incidence of renal damage in human immunodeficiency virus (HIV)-positive patients treated with TDF and to identify associated potential risk factors.

SETTING: A public university tertiary 450-beds hospital in Spain.

METHOD: Retrospective, longitudinal observational study that included adult HIV-1-infected patients treated with TDF. Patient´s treated with TDF from January 2010 to December 2012 were included. Patient follow-up started when initiating treatment with TDF up until either end of treatment or end of study (July 31, 2013). The estimated glomerular filtration rate was calculated using the four-variable modification of diet in renal disease. Renal toxicity was classified as moderate [estimated glomerular filtration rate (eGFR) < 60 ml/min] or severe (eGFR < 30 ml/min). The incidence rate for moderate and severe renal insufficiency was calculated as number of cases per 1000 patient-year. A univariate analysis and binary logistic regression was carried out in order to identify risk factors associated with renal toxicity by using the forward stepwise method (likelihood ratio)

MAIN OUTCOME MEASURE: Incidence rate for moderate and severe renal insufficiency (RI) RESULTS: 451 patients were included in the study. The incidence rate of moderate RI was 29.2 cases per 1000 person-year (95% CI 22.1-36.3), whereas the incidence of severe RI was 2.2 cases per 1000 person-year (95% CI 0.3-4.1). Multivariate analysis confirmed an independent association with the risk of kidney damage for age (OR 1.08 95% CI 1.05-1.12), time on treatment with TDF (OR 1.16 95% CI 1.04-1.30), baseline creatinine (OR 49.80 95% CI 7.90-311.92) and treatment with NNRTIs (OR 0.45 95% CI 0.24-0.83).

CONCLUSION: Mild to moderate renal failure is a frequent complication during treatment with TDF although severe renal impairment is scarce. Risk factors include age, duration of treatment with TDF, elevated baseline creatinine levels, and treatment with protease inhibitor boosted with ritonavir combinations.