Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review

Abstract

Introduction: Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV. Methods: We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009-March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0-19 years. Results and discussion: Overall 3626 abstracts and 371 full papers were screened. Four single-arm, innovator-funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment-experienced and virally suppressed children or adolescents. One trial also included treatment-naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment-naïve participants were virally suppressed (one trial). Among treatment-experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug-related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug-related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z-score (height-and age-adjusted) from baseline to 48 weeks was −0.12 (interquartile range [IQR] −0.46, 0.17) to 0.05 (IQR not reported) for spine, and −0.09 (IQR −0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight-for-age z-scores increased by 0.25 from baseline to 48 weeks. Conclusions: Four single-arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF-containing regimens over 24-48 weeks. However, further comparative and longer-term safety data are needed in children and adolescents, including on weight and metabolic changes.

Second-line tenofovir alafenamide for children with HIV in Africa

“…The superior viral suppression of 89.4% at 96 weeks observed with TAF/FTC is comparable to the 93-100% reported in four small single-arm paediatric trials of TAF conducted in Africa, Asia and North America. 12 Of note, over 85% were virologically suppressed at baseline in these studies, whereas all children in CHAPAS-4 had VL >400c/ml at baseline. Our results are also similar to the 86-92% viral suppression rates observed on TDF and TAF in the adult African NADIA and VISEND trials respectively, 6,7 and the 84-86% VL suppression at 96 weeks observed in a pooled analysis of TDF/TAF in 14 adult trials.…”

Development and emerging trends of drug resistance mutations in HIV: a bibliometric analysis based on CiteSpace

“…A recent report on use of RPV for treatment of HIV-positive adolescents revealed that while the effectiveness of RPV decreased with prolonged use, its safety remained stable ( Lombaard et al, 2022 ). In addition, TAF-containing regimens have been demonstrated to be a not-to-be-ignored strategy for children ( O'Rourke et al, 2023 ). When second-line ART is begun in children, their CD4+ T lymphocyte count increases, and their mortality and loss to follow-up decrease ( Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration, 2020 ).…”

“…Nevertheless, TAF-containing regimens are thought to provide safe and effective viral suppression for children and teenagers. This is a helpful reminder since there are few available drugs (Agwu et al, 2014;O'Rourke et al, 2023). As a tricyclic carbamoyl pyridone analog, DTG is absorbed and spread through cerebrospinal fluid and impairs the HIV integrase-DNA complex through chemical synthesis (Kandel and Walmsley, 2015).…”