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.
PrEP in pregnancy
adolescence
intracellular TFV-DP
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
05 10 2021
05 10 2021
Historique:
received:
21
09
2020
pubmed:
21
12
2020
medline:
21
10
2021
entrez:
20
12
2020
Statut:
ppublish
Résumé
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). 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. 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. 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. NCT03386578.
Sections du résumé
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.
Identifiants
pubmed: 33341883
pii: 6042339
doi: 10.1093/cid/ciaa1872
pmc: PMC8492211
doi:
Substances chimiques
Anti-HIV Agents
0
Organophosphates
0
tenofovir diphosphate
0
Adenine
JAC85A2161
Banques de données
ClinicalTrials.gov
['NCT03386578']
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1893-e1900Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI068632
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069530
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069518
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069436
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069436
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275201800001I
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068632
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275201800001C
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069463
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068616
Pays : United States
Organisme : NIH HHS
ID : UM1AI068632
Pays : United States
Investigateurs
Vongai Chanaiwa
(V)
Suzen Maonera
(S)
Lucia Mungate
(L)
Sharon Kunkanga Mambiya
(SK)
Abigail Mnemba
(A)
Flora Chithila
(F)
Phionah Nakabuye
(P)
Muzamil Nsibuka Kisekka
(MN)
Victoria Ndyanabangi
(V)
Brenda Gati Mirembe
(BG)
Phionah Kibalama Ssemambo
(PK)
Annette Miwanda Ssekasi
(AM)
Elizea Horne
(E)
Siphokazi Sibisi
(S)
Janet Grab
(J)
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
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