Faculty of Medicine, Imperial College London.
MetaVirology LTD London.
AIDS. 2020 Dec 1;34(15):2259-2268. doi: 10.1097/QAD.0000000000002699.
Both tenofovir disoproxil fumarate (TDF)/emtricitabine and tenofovir alafenamide (TAF)/emtricitabine demonstrate excellent efficacy and safety overall, but concerns remain over specific changes in markers of bone and renal function. Lower plasma tenofovir concentrations are seen with TAF and in unboosted regimens. We assess TAF vs. TDF safety with and without booster coformulation.
A previous systematic review was updated with recent clinical trials. TAF vs. TDF efficacy and safety were compared in boosted and unboosted subgroups. Efficacy was measured by viral suppression. Key safety endpoints included all adverse events, serious adverse events, Grades 3-4 adverse events and adverse event discontinuation. Further specific renal and bone markers were also assessed.
A total of 14 clinical trials comparing TDF and TAF regimens were identified. A significant difference (P = 0.0004) in efficacy was shown in the boosted subgroup in favour of TAF, but no difference was seen in the unboosted subgroup. There were no significant differences between TAF and TDF for any of the key safety endpoints analysed. No differences were seen for the bone markers analysed. No difference was found for renal tubular events. There was a difference in risk for discontinuation due to renal adverse events when boosted (P = 0.03), but none when unboosted.
Across all main safety endpoints, no differences between TAF and TDF are seen. Boosted TDF regimens were associated with lesser comparative efficacy than boosted TAF and a higher risk of renal event discontinuation. However, modern antiretroviral regimens are more commonly unboosted. This study finds no difference in efficacy or safety in unboosted TAF vs. TDF.
富马酸替诺福韦二吡呋酯（TDF）/恩曲他滨和替诺福韦艾拉酚胺（TAF）/恩曲他滨在总体上均表现出优异的疗效和安全性，但人们仍然对骨和肾功能标志物的特定变化感到担忧。与 TDF 相比，TAF 的血浆替诺福韦浓度较低，且在未增强方案中也是如此。我们评估了有无增效剂联合用药时 TAF 与 TDF 的安全性。
对先前的系统评价进行了更新，纳入了最近的临床试验。比较了 TAF 与 TDF 在增强和未增强亚组中的疗效和安全性。通过病毒抑制来衡量疗效。主要安全性终点包括所有不良事件、严重不良事件、3-4 级不良事件和因不良事件停药。还进一步评估了特定的肾脏和骨骼标志物。
共确定了 14 项比较 TDF 和 TAF 方案的临床试验。在增强亚组中，TAF 的疗效明显优于 TDF（P = 0.0004），但在未增强亚组中未见差异。在分析的所有主要安全性终点中，TAF 与 TDF 之间均无显著差异。分析的骨骼标志物未见差异。肾小管事件无差异。增强时因肾脏不良事件停药的风险存在差异（P = 0.03），但未增强时无差异。
在所有主要安全性终点中，TAF 与 TDF 之间未见差异。与增强 TAF 相比，增强 TDF 方案的疗效较差，且因肾脏事件停药的风险较高。然而，现代抗逆转录病毒方案更常为未增强方案。本研究发现，未增强 TAF 与 TDF 相比，在疗效或安全性方面无差异。
