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
| Autor: | Impaact P s Protocol Team, Kathryn Lypen, Violet Korutaro, Sybil G. Hosek, Benjamin Johnston, Deborah Kacanek, Mustafa E Ibrahim, K. Rivet Amico, Lynda Stranix-Chibanda, James F. Rooney, Nahida Chakhtoura, Hans M. L. Spiegel, Jenna Yager, Teacler Nematadzira, Clemensia Nakabiito, Lubbe Wiesner, Maysebole Masenya, Emily Brown, Sharon Huang, Peter L. Anderson, Benjamin H. Chi, Frank Taulo |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_specialty Adolescent Anti-HIV Agents Population Renal function HIV Infections Emtricitabine Medication Adherence Young Adult 03 medical and health sciences Pre-exposure prophylaxis 0302 clinical medicine Pharmacokinetics Pregnancy intracellular TFV-DP medicine Humans 030212 general & internal medicine PrEP in pregnancy Online Only Articles education Africa South of the Sahara education.field_of_study Obstetrics business.industry Adenine Postpartum Period medicine.disease 030112 virology Organophosphates HIV/AIDS Collection AcademicSubjects/MED00290 Infectious Diseases Gestation Female Pre-Exposure Prophylaxis adolescence business Postpartum period medicine.drug |
| Zdroj: | Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America |
| ISSN: | 1537-6591 1058-4838 |
| DOI: | 10.1093/cid/ciaa1872 |
| Popis: | 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 Concentrations of tenofovir diphosphate in dried blood spots were approximately one-third lower during pregnancy than postpartum after 12 weeks of directly observed dosing among African adolescent girls and young women on daily pre-exposure prophylaxis. We recommend population-specific benchmarks for adherence support. |
| Databáze: | OpenAIRE |
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