Evaluation of pharmacokinetics of Tenofovir Alafenamide (TAF) and Tenofovir Disoproxil (TDF) in pregnant and postpartum women in South Africa: PrEP-PP PK study

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2024-09-25 DOI:10.1016/j.antiviral.2024.106014

Dvora Joseph Davey , Sumaya Dadan , Kalisha Bheemraj , Catriona Waitt , Saye Khoo , Landon Myer , Lubbe Wiesner , Laura Else , Beth Thompson , Sandra Castel , Nafisa Wara , Peter L. Anderson , Catherine Orrell

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引用次数: 0

Abstract

Background

There are few data on tenofovir-diphosphate (TFV-DP) concentrations in pregnant and postpartum women on Tenofovir Disoproxil Fumarate-Emtricitabine (TDF-FTC) or Tenofovir Alafenamide-Emtricitabine (TAF-FTC).

Methods

Eligible pregnant women were randomized to TDF-FTC or TAF-FTC and followed for 16 weeks (8-weeks pregnant, 8-weeks postpartum) with weekly collection of dried blood spot (DBS) and 4-weekly peripheral blood mononuclear cells (PBMC). PrEP dosing was observed daily via asynchronous videos sent via cell phone. We report geometric means (GM) and their ratios (GMR) with 95% confidence intervals (CIs) for TFV-DP in PBMC and DBS from pregnancy and postpartum.

Results

We enrolled N = 39 participants (n = 19 TDF-FTC, n = 20 TAF-FTC): median age was 28 years (IQR:25–34); median gestational age was 24-weeks (IQR:21–28). For TDF-FTC, TFV-DP DBS concentrations at 8-weeks did not differ significantly between pregnancy (GM: 675; 95%CI:537–849) and postpartum (GM: 583; 95%CI:471–722; GMR-TDF = 1.16; 95%CI:0.74–1.80). For TAF-FTC, TFV-DP DBS concentrations at 8-weeks were 44% higher in postpartum (GM: 1199; 95%CI:929–1549) versus pregnancy (GM: 832; 95%CI:751–922; GMR-TAF = 1.44; 95% CI: 1.01–2.06). In PBMC analysis of TDF-FTC, 8-week median TFV-DP (pmol/10^6 cell) was 71 (IQR 44–112) in pregnancy and 73 (IQR 50–102) in postpartum (GMR = 1.04; 95%CI:0.44–2.44). In TAF-FTC, median PBMC at 8-weeks was 580 (IQR:341–985) in pregnancy and 666 (IQR:396–1123) in postpartum (GMR = 1.15; 95%CI:0.30–2.49).

Conclusion

TFV-DP concentrations were overall lower during pregnancy than postpartum for TAF-FTC. We found high concentrations of TFV-DP in PBMC in pregnancy and postpartum on TAF-FTC, suggesting PrEP efficacy is maintained. Efficacy and safety studies are warranted to evaluate TAF-FTC for PrEP in pregnant and postpartum women.

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评估南非孕妇和产后妇女服用替诺福韦-阿拉非那胺 (TAF) 和替诺福韦酯 (TDF) 的药代动力学：PrEP-PP PK 研究。

背景：关于服用富马酸替诺福韦二吡呋酯-恩曲他滨（TDF-FTC）或替诺福韦阿拉非那胺-恩曲他滨（TAF-FTC）的孕妇和产后妇女体内替诺福韦-二磷酸（TFV-DP）浓度的数据很少：将符合条件的孕妇随机分为 TDF-FTC 或 TAF-FTC，并进行为期 16 周的随访（怀孕 8 周，产后 8 周），每周采集一次干血斑 (DBS)，每 4 周采集一次外周血单核细胞 (PBMC)。每天通过手机发送异步视频观察 PrEP 服药情况。我们报告了孕期和产后 PBMC 和 DBS 中 TFV-DP 的几何平均数（GM）及其比率（GMR），以及 95% 的置信区间（CI）：我们招募了 N=39 名参与者（n=19 名 TDF-FTC，n=20 名 TAF-FTC）：中位年龄为 28 岁（IQR:25-34）；中位胎龄为 24 周（IQR:21-28）。对于 TDF-FTC，8 周时的 TFV-DP DBS 浓度在孕期（GM：675；95%CI：537-849）和产后（GM：583；95%CI：471-722；GMR-TDF=1.16；95%CI：0.74-1.80）没有显著差异。对于 TAF-FTC，产后（GM：1199；95%CI：929-1549）与孕期（GM：832；95%CI：751-922；GMR-TAF=1.44；95%CI：1.01-2.06）相比，8 周时的 TFV-DP DBS 浓度高出 44%。在对 TDF-FTC 的 PBMC 分析中，妊娠期 8 周的 TFV-DP 中位数（pmol/10ˆ6 细胞）为 71（IQR 44-112），产后为 73（IQR 50-102）（GMR=1.04；95%CI：0.44-2.44）。在 TAF-FTC 中，妊娠期 8 周的 PBMC 中位数为 580（IQR:341-985），产后为 666（IQR:396-1123）（GMR=1.15；95%CI:0.30-2.49）：TAF-FTC的TFV-DP浓度在孕期总体低于产后。我们发现孕期和产后服用 TAF-FTC 的 PBMC 中 TFV-DP 浓度较高，这表明 PrEP 的疗效得以保持。有必要进行疗效和安全性研究，以评估 TAF-FTC 在孕妇和产后妇女中的 PrEP 疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.