Tenofovir-associated renal dysfunction in clinical practice: An observational cohort from western India

Abstract

Background:Tenofovir (TDF) is preferred nucleoside reverse transcriptase inhibitors (NRTI) for the treatment of human immunodeficiency virus infection because of its potency and safety. Renal toxicity with TDF use is low and comparable with other NRTI in clinical trials, but there are many case studies and small case series of renal dysfunction with TDF.Materials and Methods:This is an observational longitudinal cohort of patients started on a TDF-based regimen from January 2007 to April 2010. Patients were evaluated at baseline and with every follow-up visit for serum creatinine and calculated creatinine clearance (Cockroft-Gault formula). In addition to this, the patients were also subjected to test for serum potassium, phosphorous and urine examinations as and when indicated. Renal dysfunction was defined as rise in serum creatinine to more than the upper level of normal (>1.2 mg%).Results:Of 1,271 patients started on a TDF-containing antiretroviral treatment (ART) 83 (6.53%) developed renal dysfunction, of which 79 had impaired serum creatinine and five had Fanconi’s syndrome. Renal dysfunction was more common with boosted a protease inhibitor (PI) (9.44%)-based regimen as compared to a non- nucleoside reverse transcriptase inhibitors (NNRTI) (5.01%)-based regimen (P = 0.003). The mean decline in creatinine clearance from baseline was 22.27 ml/min. The median time to develop renal dysfunction was 154 (15–935) days. Serum creatinine returned to normal in all the patients after stopping TDF. Five patients presented with features suggestive of Fanconi’s syndrome without alteration in serum creatinine.Conclusion:TDF-based treatment is associated with mild but reversible renal dysfunction. Patients receiving PI/r are at a higher risk of renal dysfunction compared to those receiving NNRTI-based ART. Clinicians should be adviced to have intensive renal monitoring, including creatinine clearance, urine examination, K+ and phosphate levels at baseline and during treatment with TDF.

The effect of Tenofovir on renal function among Ugandan adults on long-term antiretroviral therapy: a cross-sectional enrolment analysis

“…Similarly, a 10 year follow-up cohort study of HIV-positive patients, reported that the quantified loss in eGFR attributable to Tenofovir was relatively modest after many years of exposure [12]. Since the majority of our patients had been on ART for more than 9 years, our failure to find an association between renal dysfunction and duration on Tenofovir containing ART can be explained by previous studies that reported that the loss in eGFR attributable to Tenofovir seemed to occur during the first years of exposure between 0.5 and 31.2 months and stabilized after that [16, 17, 25–28]. Post marketing studies reported advanced age, low body weight, comorbidities such as diabetes mellitus, hypertension, as some of the risk factors for Tenofovir induced renal dysfunction [27, 29, 30].…”

“…In a Canadian cohort, renal dysfunction was observed in the early years of exposure to Tenofovir but the risk remained minimal beyond 6 years [12]. The median time to develop Tenofovir renal dysfunction was estimated at 154 (15–935) days in a clinical practice in western India [16]. Others have reported that tubular dysfunction or renal failure was diagnosed 6.89 ± 5.51 months after starting Tenofovir [17].…”

Incidence and Risk Factors of Renal Impairment in Hiv-1 Infected Patients Receiving Tenofovir Based Antiretroviral Therapy in a South Indian Hospital

“…The possible risk factors associated in the study group was CD4>200 (P=0.003); further details on risk factors were shown in table 2. [15]. Patients with raise in serum creatinine were largely asymptomatic, however patient with acute renal failure had presented with weakness, body pain and vomiting.…”

Renal Dysfunction among HIV-infected Patients on Tenofovir-Based Antiretroviral Therapy at Ronald Ross Hospital in Zambia

“…TDF currently is a recommended first-line agent in combination with other antiretroviral drugs for HIV management in Zambia. This is because of its favorable pharmacokinetic profile, good antiviral potency and high tolerability [3,7]. The high number of renal dysfunction cases missed at initiation and follow up suggests that screening of patients prior to initiation is rare.…”

“…TDF is an oral prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor (NRTIs) that has been indicated for use from many randomized trials [1,[4][5][6] because of its favorable pharmacokinetic profile, availability as a once-daily fixed dose, good antiviral potency and high tolerability [3,7]. TDF has been considered safe and associated with fewer side-effects in many clinical trials [4,5,8].…”