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

作者：Lynda Stranix‐Chibanda, Peter L. Anderson, Deborah Kacanek, Sybil Hosek, Sharon Huang, Teacler Nematadzira, Frank Taulo, Violet Korutaro, Clemensia Nakabiito, Maysebole Masenya, Kathryn Lypen, Emily Brown, Mustafa E. Ibrahim, Jenna Yager, Lubbe Wiesner, Benjamin Johnston, K. Rivet Amico, James F. Rooney, Nahida Chakhtoura, Hans Spiegel, Benjamin H Chi, IMPAACT 2009 Team, Vongai Chanaiwa, Suzen Maonera, Lucia Mungate, Sharon Kunkanga Mambiya, Abigail Mnemba, Flora Chithila, Phionah Nakabuye, Muzamil Nsibuka Kisekka, Victoria Ndyanabangi, Brenda Gati Mirembe, Phionah Kibalama Ssemambo, Annette Miwanda Ssekasi, Elizea Horne, Siphokazi Sibisi, Janet Grab · 发表于：Clinical Infectious Diseases · 年份：2020 · DOI：10.1093/cid/ciaa1872 · 被引用次数：66 · 研究领域：HIV/AIDS Research and Interventions、Biosimilars and Bioanalytical Methods、HIV/AIDS drug development and treatment

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 wit...