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Clinical Trial
. 2021 Oct 5;73(7):e1893-e1900.
doi: 10.1093/cid/ciaa1872.

Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa

Lynda Stranix-Chibanda  1   2 , Peter L Anderson  3 , Deborah Kacanek  4 , Sybil Hosek  5 , Sharon Huang  4 , Teacler G Nematadzira  2 , Frank Taulo  6 , Violet Korutaro  7 , Clemensia Nakabiito  8 , Maysebole Masenya  9 , Kathryn Lypen  10 , Emily Brown  10 , Mustafa E Ibrahim  3 , Jenna Yager  3 , Lubbe Wiesner  11 , Benjamin Johnston  12 , K Rivet Amico  13 , James F Rooney  14 , Nahida Chakhtoura  15 , Hans M L Spiegel  16 , Benjamin H Chi  17 ; IMPAACT 2009 Team
Collaborators, Affiliations
Clinical Trial

Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa

Lynda Stranix-Chibanda et al. Clin Infect Dis. .

Abstract

Background: Intracellular tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is used to monitor cumulative pre-exposure prophylaxis (PrEP) adherence. We evaluated TFV-DP in DBSs following daily oral PrEP (emtricitabine 200 mg/tenofovir diphosphate 300 mg) among pregnant and postpartum adolescent girls and young women (AGYW).

Methods: Directly observed PrEP was administered for 12 weeks in a pregnancy (14-24 weeks' gestation, n = 20) and postpartum (6-12 weeks postpartum, n = 20) group of AGYW aged 16-24 years in sub-Saharan Africa. Weekly DBS TFV-DP was measured by validated liquid chromatography-tandem mass spectrometry assay. Week 12 TFV-DP distributions were compared between groups with Wilcoxon test. Population pharmacokinetic models were fit to estimate steady-state concentrations and create benchmarks for adherence categories. Baseline correlates of TFV-DP were evaluated.

Results: Median age was 20 (IQR, 19-22) years. Of 3360 doses, 3352 (>99%) were directly observed. TFV-DP median (IQR) half-life was 10 (7-12) days in pregnancy and 17 (14-21) days postpartum, with steady state achieved by 5 and 8 weeks, respectively. Observed median (IQR) steady-state TFV-DP was 965 fmol/punch (691-1166) in pregnancy versus 1406 fmol/punch (1053-1859) postpartum (P = .006). Modeled median steady-state TFV-DP was 881 fmol/punch (667-1105) in pregnancy versus 1438 fmol/punch (1178-1919) postpartum. In pooled analysis, baseline creatinine clearance was associated with observed TFV-DP concentrations.

Conclusions: TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. These Population-specific benchmarks can be used to guide PrEP adherence support in pregnant/postpartum African women.

Clinical trials registration: NCT03386578.

Keywords: PrEP in pregnancy; adolescence; intracellular TFV-DP.

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Figures

Figure 1.
Figure 1.
Observed and fitted TFV-DP concentrations in pregnant and postpartum women by study week (A and B, observed; C and D, modeled). Dashed line = USA median; gray shading represents the 95% confidence interval for Loess curve. Abbreviation: TFV-DP, tenofovir diphosphate.
Figure 2.
Figure 2.
Proposed adherence thresholds for study groups. Abbreviations: DBS, dried blood spot; ROC, receiver operating characteristic curve; TFV-DP, tenofovir diphosphate.
See this image and copyright information in PMC

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