Q6. Safety: Is TAF associated with weight gain?

Safety:
Is TAF associated with weight gain?

TDF 與 TAF 皆為 TFV 的前驅藥，但兩者對血脂與體重的影響不同
TDF and TAF are both TFV prodrugs with different effect on lipid and weight profiles.
- TDF 與血脂檢驗值、體重減少有關 ^1-6。
  TDF is associated with a decrease of lipid laboratory values and a suppressive effect on weight.^1-6
- 在不同的族群中，例如 HBV 病人 HIV 預防投藥之健康人和 HIV 病人，使用 TAF 對血脂、體重的影響很小 ^1,3,7-9。
  TAF is lipid-neutral with minimal effects on weight as shown in multiple studies in various populations, including HBV infected individuals, healthy individuals taking TAF as part of HIV prevention strategy, and people living with HIV. ^1,3,7-9
- 研究顯示過去使用 TDF 的病人改以 TAF 治療後，在失去 TDF 作用的情況下，血脂指數皆有所增加 ^3,7,8,10,11。
  Studies that switch patients from TDF to TAF based regimens often show an increase in lipid fractions and weight due to the loss of the effect of TDF on these parameters. ^3,7,8,10,11
多項臨床試驗針對 B 型肝炎病毒血症以及病毒受到抑制的慢性 B 型肝炎病人，評估使用 TAF 後空腹血脂與體重的變化：
Fasting lipids and weight changes with TAF use were evaluated in viremic and virologically-suppressed chronic hepatitis B patients:
- 108/110 試驗：兩項第三期臨床試驗的 5 年結果，目前試驗仍執行中 ⁷；4018 試驗：為期 2 年的第三期臨床試驗，患者自 TDF 改為 TAF ^8,10；4035 試驗：針對肝、腎功能不全的患者的第二期臨床試驗的 1 年結果 ^12,13。
- For 5 years in two ongoing TAF Phase 3 registrational studies (Trial 108/110).⁷
- For 2 years in a dedicated Phase 3 TDF to TAF switch study (Trial 4018).^8,10
- For 1 year in two Phase 2 studies in patients with renal and hepatic impairment (Trial 4035).^12,13
在改為 TAF 治療後血脂與體重的變化是停用 TDF 後可預期的效應，對於大多數患者而言，這些變化可能不具有臨床意義，而可能反映出血脂、體重隨年齡增加的自然現象 ^7,9,10。
The changes in lipids and weight after switching to TAF were not unexpected and reflect the removal of the lipid-lowering and weight-suppressive effects of TDF. These changes are not likely to be clinically important for most patients and also potentially reflect a natural course of lipid and weight changes with age. ^7,9,10
上述臨床試驗顯示患者自 TDF 改為 TAF 治療後，空腹血脂和體重中位數（≤ 2 kg）均輕微上升 ^7,8,10,12,13。次族群分析顯示，在不同亞洲人種患者皆有近似的結果（Figure 1,2,3）^14,15。
In the above trials, modest increases were observed in fasting lipids and median weight (≤ 2 kg) when patients switched from TDF to TAF.^7,8,10,12,13
- Subset analysis in Asian and Asian ethnicity CHB patients demonstrated similar results.^14,15

CHB, chronic hepatitis B; ESRD, end stage renal disease; HBV, hepatitis B virus; HDL, high-density lipoprotein; HI, hepatic impairment; HIV, human immunodeficiency virus; LDL, low-density lipoprotein; OAV, oral antiviral; OL, open-label; Q, quartile; RI, renal impairment; TAF, tenofovir alafenamide; TC, total cholesterol; TDF, tenofovir disoproxil fumarate; TFV, tenofovir; TG, triglyceride; vs, versus; y, year.

References: 1. Arribas J, et al. J Acquir Immune Defic Syndr. 2017;75(2):211-218; 2. Behrens G, et al. Antivir Ther 2012; 17: 1011–20; 3. Agarwal K, et al. J Hepatol. 2018; 68(4): 672-681; 4. Randell P, et al. Antivir Ther. 2010;15(2):227-33. doi: 10.3851/IMP1518; 5. Glidden D, et al. Clin Infect Dis 2018;67:411-419; 6. Truvada Prescribing Information. Gilead Sciences. June 2020; 7. Chan HLY, et al. AASLD 2020. 803; 8. Lampertico P, et al. EASL 2020. O91; 9. Mayer KH, et al. Lancet 2020; 396: 239–54; 10. Lampertico P, et al. Lancet Gastroenterol Hepatol. 2020 May;5(5):441-453; 11. Mills A, et al. Lancet Infect Dis 2016; 16(1):43-52; 12. Lim YS, et al. EASL 2020. SAT442; 13. Janssen H, et al. EASL 2020. SAT429; 14. Ahn SH, et al. APASL 2021. H-01; 15. Wong G, et al. APASL 2021, H-18.

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