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

Antiviral Res. 2024 Nov:231:106014. doi: 10.1016/j.antiviral.2024.106014. Epub 2024 Sep 25.

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.

Keywords: Pharmacokinetics; PrEP; Pregnancy; Prevention; TAF/FTC; TDF/FTC.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adenine* / administration & dosage
  • Adenine* / analogs & derivatives
  • Adenine* / pharmacokinetics
  • Adenine* / therapeutic use
  • Adult
  • Alanine* / pharmacokinetics
  • Anti-HIV Agents* / administration & dosage
  • Anti-HIV Agents* / pharmacokinetics
  • Emtricitabine / administration & dosage
  • Emtricitabine / pharmacokinetics
  • Emtricitabine / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • Humans
  • Leukocytes, Mononuclear
  • Organophosphates
  • Postpartum Period*
  • Pre-Exposure Prophylaxis* / methods
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • South Africa
  • Tenofovir* / administration & dosage
  • Tenofovir* / analogs & derivatives
  • Tenofovir* / pharmacokinetics
  • Young Adult

Substances

  • Tenofovir
  • Anti-HIV Agents
  • tenofovir alafenamide
  • Alanine
  • Adenine
  • Emtricitabine
  • tenofovir diphosphate
  • Organophosphates