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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-02-01
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| Series: | Journal of the International AIDS Society |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jia2.26037 |
| _version_ | 1797894120229830656 |
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| author | John O'Rourke Claire L. Townsend Edith Milanzi Intira Jeannie Collins Hannah Castro Ali Judd Marissa Vicari Julie Jesson Valériane Leroy Martina Penazzato Françoise Renaud |
| author_facet | John O'Rourke Claire L. Townsend Edith Milanzi Intira Jeannie Collins Hannah Castro Ali Judd Marissa Vicari Julie Jesson Valériane Leroy Martina Penazzato Françoise Renaud |
| author_sort | John O'Rourke |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T07:03:46Z |
| format | Article |
| id | doaj.art-506a2793526a41bba159fa5b9a5617fe |
| institution | Directory Open Access Journal |
| issn | 1758-2652 |
| language | English |
| last_indexed | 2024-04-10T07:03:46Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the International AIDS Society |
| spelling | doaj.art-506a2793526a41bba159fa5b9a5617fe2023-02-27T11:46:28ZengWileyJournal of the International AIDS Society1758-26522023-02-01262n/an/a10.1002/jia2.26037Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic reviewJohn O'Rourke0Claire L. Townsend1Edith Milanzi2Intira Jeannie Collins3Hannah Castro4Ali Judd5Marissa Vicari6Julie Jesson7Valériane Leroy8Martina Penazzato9Françoise Renaud10Consultants to the World Health Organization Geneva SwitzerlandConsultants to the World Health Organization Geneva SwitzerlandMRC Clinical Trials Unit at UCL University College London London UKMRC Clinical Trials Unit at UCL University College London London UKMRC Clinical Trials Unit at UCL University College London London UKMRC Clinical Trials Unit at UCL University College London London UKInternational AIDS Society Geneva SwitzerlandCentre for Epidemiology and Research in POPulation Health (CERPOP) Inserm, Université de Toulouse Université Paul Sabatier Toulouse FranceCentre for Epidemiology and Research in POPulation Health (CERPOP) Inserm, Université de Toulouse Université Paul Sabatier Toulouse FranceHIV Department World Health Organization Geneva SwitzerlandHIV Department World Health Organization Geneva SwitzerlandAbstract 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.https://doi.org/10.1002/jia2.26037childrendrug‐related side effects and adverse reactionsHIVsystematic reviewtenofovirtreatment outcome |
| spellingShingle | John O'Rourke Claire L. Townsend Edith Milanzi Intira Jeannie Collins Hannah Castro Ali Judd Marissa Vicari Julie Jesson Valériane Leroy Martina Penazzato Françoise Renaud Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review Journal of the International AIDS Society children drug‐related side effects and adverse reactions HIV systematic review tenofovir treatment outcome |
| title | Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review |
| title_full | Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review |
| title_fullStr | Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review |
| title_full_unstemmed | Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review |
| title_short | Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review |
| title_sort | effectiveness and safety of tenofovir alafenamide in children and adolescents living with hiv a systematic review |
| topic | children drug‐related side effects and adverse reactions HIV systematic review tenofovir treatment outcome |
| url | https://doi.org/10.1002/jia2.26037 |
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