Side effects of long-term oral antiviral therapy for hepatitis B

Abstract

The aim of this review is to summarize the safety profile of the five approved oral nucleoside analogs used to treat chronic hepatitis B virus (HBV) infection, focusing on both the class adverse effects and those that have been reported with individual agents, as well as their safety in pregnancy. All nucleoside analogs have a "Black Box" warning because of their potential for inhibition of human DNA polymerase gamma involved in mitochondrial DNA replication. A reduction in intracellular mitochondrial DNA levels can lead to varying clinical manifestations of mitochondrial toxicity (i.e., neuropathy, myopathy, lactic acidosis), but these side effects are rarely reported with the oral antiviral agents active against HBV. Adefovir and tenofovir are associated with a dose-dependent but usually reversible proximal renal tubular toxicity. For these reasons, patients receiving these agents should be monitored for renal toxicity and the dose modified for renal insufficiency. Prolonged use of tenofovir has also been reported to lead to reduced bone mineral density in patients with human immunodeficiency virus infection, but prospective studies in patients with HBV infection are lacking. Telbivudine treatment is associated with moderate serum creatine phosphokinase elevations in up to 12% of patients. There have been few prospective studies on the safety of nucleoside analogs during pregnancy. According to the Antiretroviral Pregnancy Registry, the incidence of birth defects associated with lamivudine and tenofovir use during pregnancy is not increased. Studies on the safety of long-term therapy with the nucleoside analogs, alone and in combination, are needed as are further studies of children, the elderly, pregnant women, and patients with renal insufficiency. (HEPATOLOGY 2009;49: S185-S195.)

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

“…These guidelines would encompass the development of new skills and study procedures covering adherence counseling and monitoring, safety monitoring (in particular tenofovir renal 99 and bone density toxicity, 100 if TDF is used, although unlikely to be monitored in resource-limited settings), and antiretroviral drug resistance monitoring.…”

Antiviral treatment for chronic hepatitis B in renal transplant patients

“…In consequence, RT recipients may have many of these basal renal risk factors. In clinical trials outside renal transplant setting, minimal decline in renal function have been showed with all NUCs, except for LdT which appears to improve renal function [67,68] . Impact of LdT on renal function was analyzed from a database including all patients treated in the GLOBE Study (2 years), in the long term extension study CN04E1 (4 to 6 years) and in patients with decompensated cirrhosis (2 years) [69] .…”

“…Overall, some renal adverse effect was reported in 26 patients (7%) [81] . In comparison to nucleotide analogues, nucleoside analogues, such as ETV and LdT, show not significant renal toxicity [67,68] . Studies have been performed comparing ETV and TDF nephrotoxicity [82][83][84][85][86] .…”

Raltegravir-based highly active antiretroviral therapy has beneficial effects on the renal function of human immunodeficiency virus-infected patients after solid organ transplantation

“…In addition, as previously reported in pivotal trials, 13,14 RAL has an acceptable safety profile when it is combined with a variety of antiretroviral drugs, including tenofovir, a drug that is commonly used against HIV/hepatitis B virus infection and that increases the risk of renal tubular damage. 15 In conclusion, in HIV-infected subjects who undergo SOT, RAL-based, PI-sparing HAART is effective in preventing renal impairment and allows maintenance of potent and sustained antiretroviral activity. …”