A Randomized Study of Tenofovir Disoproxil Fumarate in Treatment-experienced HIV-1 Infected Adolescents

Abstract

This study of TDF in combination with an OBR in antiretroviral-experienced adolescents did not meet its primary or secondary efficacy endpoints. The effectiveness of the OBR and baseline genotypic resistance to TDF in both groups may have confounded the efficacy findings. No clinically relevant TDF-related renal or bone toxicities were observed in this adolescent population.

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

“…Irreversible renal failure has been reported in an adolescent with an underlying kidney disease and who was treated with a tenofovir regimen including ritonavir-boosted lopinavir but without didanosine [35]. It is important to note that the RCTs [23,24] included in this review typically combined TDF with non-NRTI-based ART (rather than a ritonavir-boosted regimen and/ or didanosine). The most commonly reported TDF-associated bone adverse effects was low BMD, which was seen in over 60% of studies.…”

“…This was a challenge as TDF was previously only available as a once-daily adult dose of 300 mg, but the children's formulation has now been made available by the manufacturer. Several studies [11,14,23,24,[26][27][28]38] have examined the effect of TDF on kidney function in HIVinfected children, including the two RCTs, with variable reports of evidence of renal impairment (including a decrease in glomerular filtration rate, hypophosphatemia, and proximal tubule dysfunction). In general, most of the studies have small sample sizes and are non-comparative, suggesting the need for adequately powered RCTs.…”

“…There were twelve reported renal and bone adverse effects due to TDF-based regimen in these studies (four renal and eight bone adverse effects) and a total of 11 participants were affected by these adverse effects. One RCT was aimed at the efficacy and safety of TDF in combination with an optimized background regimen (OBR) in treatment-experienced HIV-1 infected adolescents (12 to <18 years) with viremia despite antiretroviral treatment [23] and the other assessed the efficacy and safety of TDF in virologically suppressed, treatment-experienced HIV-infected children ages 2 to <16 years [24]. The study of Negra et al [23],…”

“…Nineteen studies (two RCTs [23,24], nine non-randomised and observational studies [9,10,14,15,[25][26][27][28][29], four case reports [12,[30][31][32] and four case series [13,[33][34][35]) that reported the presence of renal and bone adverse effects of TDF-containing regimen were identified, including a total of 1100 study participants. The various study designs for the non-randomised and observational studies included, three single arm open label trials [9,14,15], two retrospective cohorts studies [10,25], one cross-sectional evaluation study [26] and three prospective cohort studies [27][28][29], of which one involved retrospective and prospective data collections in a two-phase design.…”

“…The data on renal and bone adverse effects of TDF-containing regimen were identified and extracted from two RCTs [23,24] which had a total of 187 study participants. There were twelve reported renal and bone adverse effects due to TDF-based regimen in these studies (four renal and eight bone adverse effects) and a total of 11 participants were affected by these adverse effects.…”