Discontinuation Of Tenofovir Research Articles

Severe Acute Renal Failure in an HIV-Infected Patient After Only 2 Weeks of Tenofovir-Based Antiretroviral Therapy

We report a 46-year-old man who has sex with men (MSM) patient, of Scottish descent, who had no history of arterial hypertension, diabetes, or illicit drug use, was hepatitis C virus (HCV) negative but underwent right nephrectomy for urothelial tumor in 2006. Before starting antiretroviral therapy, he had a CD4 cell count of 316/mm(3) and plasma HIV RNA level was 1,020,537 copies per milliliter. He developed acute renal failure only 2 weeks after introduction of tenofovir-based antiretroviral therapy and then required 3 months of hemodialysis. After the end of hemodialysis, antiviral therapy was resumed with abacavir (300 mg×2/day), lamivudine (300 mg every day), and lopinavir/ritonavir (400/100 mg twice daily). Renal biopsy revealed severe and diffuse toxic acute tubular necrosis Two years after tenofovir discontinuation, the patient's renal function remained subnormal. Although severe renal toxicity due to tenofovir is rare, patients receiving tenofovir must be monitored closely for renal dysfunction especially during the first weeks of tenofovir therapy.

A Comparison of Tenofovir-Associated Renal Function Changes in HIV-infected African Americans vs Caucasians

The effects of tenofovir on renal function have been measured in multiple studies. Although African Americans are at a higher risk of developing chronic kidney disease, there are limited data examining the influence of race on tenofovir-related nephrotoxicity. This was a retrospective study of human immunodeficiency virus (HIV)-infected patients at a university-affiliated HIV clinic who were prescribed tenofovir between July 1, 2001, and January 31, 2009. The primary outcome was mean change in creatinine clearance. Secondary endpoints assessed the odds of tenofovir discontinuation secondary to nephrotoxicity, and prevalence of grade 2 to 4 serum creatinine elevation and hypophosphatemia during treatment. A total of 65 African American and 186 Caucasian patients were included. There were no statistically significant differences in mean change in creatinine clearance, as estimated by the Cockcroft-Gault (-14.2 mL/min vs -15.9 mL/min [P = .525]) and modification of diet in renal disease formulas (-17.2 mL/min/1.73 m2 vs -15.6 mL/min/1.73 m2 [P = .585]) between African Americans and Caucasians. Rates of tenofovir discontinuation secondary to nephrotoxicity were 6.2% and 1.6%, respectively (P = .076). Elevated baseline serum creatinine and female gender may be potential predictors for tenofovir discontinuation. There were no statistically significant differences in tenofovir-related renal function changes by race as observed in our HIV patient population.

Normal plasma FGF23 levels kinetic in tenofovir-related hypophosphatemic osteomalacia in an HIV-infected patient with von Recklinghausen disease

The antiretroviral agent tenofovir can cause hypophosphatemic osteomalacia due to renal phosphate wasting. The potential role for Fibroblast Growth Factor 23 (FGF23), a phosphaturic hormone is unknown. We evaluated FGF23 plasma concentrations in an HIV-positive patient with neurofibromatosis in whom hypophosphatemia developed during tenofovir therapy. This patient presented with diffuse pain, hypophosphatemia and tubular dysfunction with inadequate phosphate reabsorption. The full recovery after tenofovir discontinuation indicates that the hypophosphatemia was related to tenofovir and not to von Recklinghausen disease. Our data argue against a role for FGF23 in tenofovir-induced hypophosphatemia nor in the regulation of hypophosphatemia in this situation.

Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities

Tenofovir, a widely prescribed antiretroviral medication for treatment of HIV-1 infection, is infrequently associated with renal dysfunction and biopsy findings of acute tubular necrosis. We examined the clinical and pathological findings in 13 cases of tenofovir nephrotoxicity (7 men and 6 women, mean age of 51.1±9.6 years). Patients received tenofovir therapy for a mean of 19.6 months (range, 3 weeks to 8 years; median 8 months). Nine patients presented with acute kidney injury, and four had mild renal insufficiency with subnephrotic proteinuria. Mean baseline serum creatinine was 1.3±0.3 mg/dl, reaching 5.7±4.0 mg/dl at the time of biopsy, with mean proteinuria of 1.6±0.3 g/day. Glycosuria was documented in seven patients, five of whom were normoglycemic. Renal biopsy revealed toxic acute tubular necrosis, with distinctive proximal tubular eosinophilic inclusions representing giant mitochondria visible by light microscopy. Electron microscopy showed mitochondrial enlargement, depletion, and dysmorphic changes. Clinical follow-up after tenofovir discontinuation was available for 11 of 13 patients (mean duration 13.6 months). Significant recovery of renal function occurred in all patients, including four who required transient hemodialysis. Our study shows that tenofovir nephrotoxicity is a largely reversible form of toxic acute tubular necrosis targeting proximal tubules and manifesting distinctive light microscopic and ultrastructural features of mitochondrial injury.

Whole body bone scintigraphy in tenofovir-related osteomalacia: a case report

IntroductionTenofovir disoproxil fumarate (Viread®) is the only nucleotide reverse transcriptase inhibitor currently approved for the treatment of HIV. It is frequently prescribed not only for its efficacy but also for its decreased side effect profile compared with other nucleotide analogs. In addition, it is now increasingly recognized as a cause of acquired Fanconi's syndrome in individuals with HIV.Case presentationWe describe a 48-year-old woman infected with HIV, with chronic renal insufficiency, who developed Fanconi's syndrome after inclusion of tenofovir disoproxil fumarate in her antiretroviral therapy. A whole body bone scintigraphy was performed, revealing an abnormal distribution of radiotracer uptake, with characteristic changes compatible with osteomalacia. All symptoms disappeared after tenofovir discontinuation and mineral supplementation. No other explanation for the sudden and complete resolution of the bone disease was found.ConclusionThe case highlights the role of whole body bone scintigraphy in the diagnosis of tenofovir-related osteomalacia.

Effect of tenofovir subtraction on HIV plasma viraemia, CD4+ T-cell count and resistance in a patient with baseline K65R and M184V mutations

In vitro, the reverse transcriptase mutation K65R can simultaneously reduce drug susceptibility, replicative capacity and restrict HIV-1 replication. Here, we assessed the effect of tenofovir discontinuation for a patient receiving antiretroviral therapy whose HIV-1 had a dominant K65R/M184V genotype. Although limited by the single-case nature, the data support a hypothesis that there is no HIV viral RNA or CD4+ T-cell count benefit of taking tenofovir for experienced patients with genotypic evidence of K65R/M184V.

Acquired Fanconi's Syndrome Associated with Tenofovir Therapy

Tenofovir (Viread) is a nucleotide reverse transcriptase inhibitor introduced into the United States in 2001. It is frequently prescribed not only for its efficacy but also for its decreased side effect profile compared with other nucleoside analogs. It is now increasingly recognized as a cause of acquired Fanconi's syndrome (FS) in human immunodeficient individuals. We describe a case of a patient with AIDS, who, after starting tenofovir therapy, developed myalgias, renal failure, and profound electrolyte abnormalities compatible with the classic features of FS. On discontinuation of tenofovir and replacement of electrolytes, the individual improved clinically with normalization of his renal failure and electrolyte abnormalities. With the success of tenofovir in the anti-HIV drug market, practitioners should remain alert to the possibility of the development of FS. Frequent urine, renal, and electrolyte parameters should be measured at regular intervals following initiation of tenofovir therapy.

Hypokalemia in HIV patients on tenofovir

Although adverse events in HIV patients taking tenofovir are relatively rare, postmarketing reports of nephrotoxicity have alerted physicians to other potentially serious outcomes. We present a series of 40 patients who developed hypokalemia associated with tenofovir. Identified risk factors included concomitant ritonavir or didanosine use, a lower weight and longer duration of tenofovir use. Recovery or improvement was seen in the majority of patients (66%) after the discontinuation of tenofovir; however, four deaths occurred. The associated consequences of tenofovir-related hypokalemia may be profound and life-threatening.