Review of Tenofovir Use in HIV-infected Children

Abstract

Tenofovir disoproxil fumarate (TDF) is approved by the Food and Drug Administration for use in children ages 2 years and older and is recommended by the World Health Organization for use as a preferred first-line nucleotide reverse transcriptase inhibitor in adults and adolescents ages 10 years and older. The simplicity of once daily dosing, few metabolic side effects and efficacy against hepatitis B virus make TDF suitable for use in a large scale program. Unlike thymidine analoge nucleoside reverse transcriptase inhibitors (NRTIs); tenofovir does not induce multi-NRTI resistance mutations, so more NRTI options are available for future second-line-regimens. Fixed-dose combinations of TDF with other ARVs as a single tablet regimen are now widely available for adults and adolescents, but none are available for young children. Current information on TDF including the pharmacokinetics, safety and tolerability in children and adolescents was reviewed. A dosing regimen according to body-weight-band has been established for pediatric use. Safety concerns of TDF mainly relate to its effects on renal function and bone mineral density. Regular monitoring of renal function in high-risk patients, including those on other nephrotoxic drugs, may be warranted to detect adverse renal effects. Long-term-data on renal and bone outcomes among HIV-infected children is needed. Lessons learned from clinical studies will help clinicians balance the risks and benefits of TDF and design appropriate antiretroviral regimens for children in different circumstances.

Tackling virological failure in HIV-infected children living in Africa

“…tenofovir (TDF) is unavailable for children aged <2 years, but in those aged >3 years, efforts should be made to harmonize with adult practices and to use emtricitabine (FDC)-containing regimens for children, including TDF + 3TC (as FDC) to be given with EFV (triple pediatric FDC) or NVP. TDF has been associated with favorable outcomes in pediatric salvage therapy studies [72], However, it has been associated with bone mineral density loss, increased bone turnover as well as changes in serum calcium, phosphate, parathyroid hormone, vitamin D level and urinary calcium excretion in children [73][74][75]. It is advised to avoid TDF in patients with baseline renal insufficiency.…”

“…In adults, the Development of ARV Therapy in Africa trial showed small changes in glomerular filtration rates compared with other ARVs [76], although this may be because renal toxicities take a longer time to manifest. It is advised that children on TDF undergo monitoring of serum creatinine, urine glucose and urine protein approximately every 3-6 months [75]. The need for routine renal and bone density monitor may be an impediment to its routine use in resource-restricted settings and further data are needed in the pediatric setting.…”

An update on the HIV treatment cascade in children and adolescents

“…Weight band dosing in children >3 years has been shown to have good short-term safety profile with equivalent pharmacokinetics [54]. However, there are concerns regarding long-term effects on bone mineral deposition and renal toxicity [55]. Tenofovir is currently being evaluated in adolescents >12 years of age in combination with elvitegravir and with other agents [56].…”

Renal and Bone Adverse Effects of a Tenofovir-Based Regimen in the Treatment of HIV-Infected Children: A Systematic Review

“…The clinical implication of this remains unclear given the often short duration of many studies. Studies with a longer duration may be needed to evaluate clinically important complications [39].…”