Q7. Special Population:What is the pregnancy category of TAF? Is TAF safe during pregnancy and/or breastfeeding?

Special Population:
What is the pregnancy category of TAF?
Is TAF safe during pregnancy and/or breastfeeding?

依據 VEMLIDY^® 仿單與全球孕婦使用抗病毒藥物登錄系統（APR）顯示，TAF 的整體出生缺陷風險，與亞特蘭大大都會先天缺陷計劃（MACDP）中美國參考族群的重大出生缺陷背景發生率（2.7%）並無明顯差異¹。
According to the VEMLIDY US PI, available data from the APR show no significant difference in the overall risk of birth defects for TAF compared with the background rate for major birth defects of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program.²
- Exposures to TAF-containing regimens during pregnancy resulting in live births (including over 200 exposed in the first trimester and over 80 exposed in the second/third trimester), the prevalence of birth defects in live births was 5.2% (95% CI: 2.7% to 8.8%) and 1.2% (95% CI: 0% to 6.5%) following first and second/third trimester exposure, respectively, to TAF-containing regimens.²
中國一項多中心單臂回溯性的世代研究，針對 HBeAg (+)、HBV DNA > 200,000 IU/mL 的孕婦，觀察 TAF 使用於第 2 - 3 孕期的效果 ³。
A multicenter, single arm, retrospective national cohort study in China done by Ding el al., looked at the use of TAF in the third trimester in 71 HBeAg (+) females with an HBV DNA >200,000 IU/mL. All mothers received TAF in second and third trimesters with a mean of 13 weeks prior to delivery.³
- 在產後 24 – 28 週，沒有任何新生兒測得 HBV DNA 或 HBsAg (+) 。
  At weeks 24-28 weeks post-delivery, no infants had detectable HBV DNA or HBsAg (+) .
- TAF 可有效預防母子垂直傳染，且不會造成母嬰雙方的不良事件或畸形。
  TAF in highly viremic mothers was effective at preventing MTCT without maternal or infant AE/malformation.
另一項中國的多中心、前瞻性觀察型研究，探討 TAF 對於預防母子垂直傳染 HBV 的效益與安全性，其結果於美國肝臟研究學會（AASLD）2020 年會上發表 ⁴。
Another recent Chinese, multi-center, prospective, observational study investigating the safety and efficacy of TAF in preventing MTCT of HBV in pregnant women was presented at AASLD in 2020.⁴
- 所有孕婦在生產時，體內 HBV DNA 皆 < 200,000 IU/mL。
  At delivery, all mothers achieved an HBV DNA level < 200,000 IU/ml (none achieved HBeAg or HBsAg loss).
- 所有新生兒在 7 個月時的 HBsAg 陽性率為 0%。
  The HBsAg positive rate was 0% at 7 months in all infants.
- 全部 117 位新生兒皆無出生缺陷；7 個月大時的生理與神經學發展均符合中國與世界衛生組織（WHO）的標準。
  117 infants were born, no infants had birth defects, and the infants’ physical and neurological development at birth and at 7 months were comparable with the China national and WHO standards.
依據 VEMLIDY^® 仿單，目前並不確知 TAF 及其代謝物是否會出現於人類的乳汁中、影響乳汁生成作用或對餵哺母乳的嬰兒造成影響。應一併考慮餵哺母乳對於發育與健康之效益、母親對 VEMLIDY^® 的臨床需求，以及 VEMLIDY® 或母親的基礎疾病對餵哺母乳之嬰兒的任何可能不良影響（Table 1）^1,5。
It is unknown whether TAF and its metabolites are present in human breast milk, affect human milk production, or have effects on the breastfed infant.² The developmental and health benefits of breastfeeding vs potential risks should be discussed between HCPs and patients.⁶

依據 VEMLIDY^® 仿單，在大鼠與兔子的動物實驗中，施予 51 倍人類每日建議劑量的 TAF，並未發現任何胚胎胎兒不良影響¹。
TAF was administered to pregnant rats and rabbits. There were no adverse effects observed in the embryo or fetus at TAF exposures up to 51 times higher than the recommended human daily dose.²
有 11 位母親在哺乳期間使用 TDF 達 1 個月以上，其嬰兒的血漿 TFV 濃度均為 0 ng/mL⁷。
In mothers (N=11) who received TDF for at least 1 month during the breastfeeding period, TFV concentrations in all the infant plasma samples were 0 ng/mL.⁷
The FDA has changed how they describe the risks and benefits of drug use in pregnancy and breastfeeding, and has moved away from lettered categories. The only TAF-regimen which received a pregnancy category prior to the change was E/C/F/TAF with a category B designation (original PI).^8,9
在一中國單中心、隨機分派對照試驗研究中，比較 TAF 與 TDF 對於預防母子垂直傳染 HBV 的效益與安全性，其結果顯示 TAF 在母親之臍帶血與母乳中的藥物濃度皆 < 1.00 ng/mL，且顯著低於 TDF 在母親之臍帶血與母乳中的藥物濃度 ¹⁰。

AASLD, American Association for the Study of Liver Diseases; AE, adverse event; APR, Antiretroviral Pregnancy Registry; ARV, antiretroviral; CDC, Centers for Disease Control and Prevention; CI, confidence interval; DNA, deoxyribonucleic acid; E/C/F/TAF, elvitegravir / cobicistat / emtricitabine / TAF; FDA, Food and Drug Administration; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCP, healthcare provider; IU, international unit; MACDP, Metropolitan Atlanta Congenital Defects Program; MTCT, mother-to-child transmission; n/a, not applicable; PI, prescribing information; TAF, tenofovir alafenamide; TBDR, Texas Birth Defects Registry; TDF, tenofovir disoproxil fumarate; TFV, tenofovir; US, United States; vs, versus; WHO, World Health Organization.

References: 1. 韋立得膜衣錠。中文仿單［TWN-NOV20-US-FEB20-（EU-NOV17）］; 2. VEMLIDY^® [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; August 2020; 3. Ding Y, et al. Aliment Pharmacol Ther. 2020;52(8):1377-1386. doi: 10.1111/apt.16043. Epub 2020 Aug 27; 4. Zeng QL, et al. AASLD 2020. 160; 5. The Antiretroviral Pregnancy Registry: Interim Report Jan 1, 1989 through July 31,2019; 6. Terrault NB et al. Hepatology 2018; Published online February 5, 2018: doi:10.1002/hep.29800; 7. Erturk, AASLD 2018, 431; 8. GENVOYA^® [prescribing information]. Foster City, CA: Gilead Sciences, Inc.: Revised February 2016; 9. Pregnancy and Lactation Labeling (Drugs) Final Rule. FDA. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm093307.html. Published 2014. accessed December 02/2016; 10. Li B, et al. Hepatol Int. 2021;15(5):1103-1108.

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