TUAB0201 - Oral Abstract Session
Tenofovir disoproxil fumarate (TDF) pharmacokinetics (PK) with daily dosing in the first week of life (HPTN 057)
Presented by Karin Nielsen-Saines (United States).
K. Nielsen-Saines1, M. Mirochnick2, N. Kumwenda3, E.C. Joao4, R. Kreitchmann5, J. Pinto6, B. Santos7, T. Parsons8, P. Richardson8, T. Taha3, L. Mofenson9, P. Sato10, B. Kearney11, M.G. Fowler12
1David Geffen School of Medicine at UCLA, Los Angeles, United States, 2Boston University, Boston, United States, 3Johns Hopkins Bloomberg School of Public Health, Baltimore, United States, 4Hospital dos Servidores do Estado, Rio de Janeiro, Brazil, 5Irmandade da Santa Casa de Misercordia de Porto Alegre, Porto Alegre, Brazil, 6Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, 7Grupo Hospitalar Conceicao, Porto Alegre, Brazil, 8Johns Hopkins Univ. School of Medicine, Baltimore, United States, 9NICHD/PAMAB, Bethesda, United States, 10NIAID, Bethesda, United States, 11Gilead Sciences, Forest City, United States, 12Johns Hopkins Medical Institutes, Kampala, Uganda
Background: There are limited data on the pharmacokinetics (PK) of tenofovir (TFV) administered to pregnant women during labor or to newborns.
Methods: HPTN 057 is a phase I trial of tenofovir disoproxil fumarate (TDF) in HIV-infected pregnant women and their neonates in Malawi and Brazil. In the current cohort, women received 600 mg TDF at labor onset or 4 hours prior to C section (C/S) and newborns received 6 mg/kg TDF suspension daily x 7 doses. Plasma samples were obtained from mothers at delivery, from cord blood and from infants before and 2, 10 and 24 hours after the 1st, 4th and 7th doses. TFV concentration (conc) was determined by HPLC/MS/MS; lower limit of quantitation was 5 ng/mL. The PK target was to keep infant TFV conc >50 ng/ml (mean trough conc in nonpregnant adults) for the first week of life. Data are presented as median (range) or geometric mean (%CV).
Results: 33 mother-infant pairs were studied (21 vaginal deliveries, 12 C/S). Delivery occurred median of 4.5 (0.6-11.4) hours after dosing. Mean maternal TFV conc at delivery was 108 (76.1%) ng/mL. Mean cord blood TFV conc was 61 (69.3%) ng/mL. Cord blood TFV conc was > 50 ng/mL in 24/31 (77%). Mean ratio of cord blood to maternal delivery TFV conc was 0.55 (64.0%). Infant 24 hr postdose conc was > 50 ng/mL in 28/31 (90.3%) after the first dose, in 27/28 (96.4%) after the 4th dose and in 22/30 (73.3%) after the 7th dose. All infant TFV conc were >30 ng/mL. All mothers and infants tolerated TDF well.
Mean (CV%) infant PK parameters are presented below:
[Mean (CV%) infant PK parameters]
|1||288 (49.9%)||104 (47.9%)||3939 (37.6%)||13.2 (80.1%)|
|4||336 (40.5%)||112 (52.1%)||4413 (37.4%)||14.5 (45.0%)|
|7||221 (66.1%)||69.7 (45.7%)||3060 (49.0%)||14.6 (96.1%)|
Conclusions: This regimen provides TFV exposure similar to adults receiving 300 mg daily doses and is appropriate for use in neonates in studies of TDF used for HIV prophylaxis or treatment.
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