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HPTN 057
A
Phase I Open Label Trial of the Safety and Pharmacokinetics of Tenofovir
Disoproxil Fumarate in HIV-1 Infected Pregnant Women and their Infants
057Navigation
What
is HPTN 057?
Evaluation
of alternative antiretroviral agents that can be used in simple perinatal
regimens suitable for the prevention of mother to child HIV transmission
in the developing world is a high priority for the HPTN.
Tenofovir is a potent new antiretroviral with proven animal model
efficacy, a favorable resistance profile and pharmacokinetic properties
that make it attractive for use in short course regimens for prevention of
intrapartum and early postpartum/breast feeding mother to child HIV
transmission.
HPTN 057 will provide the pharmacokinetic and safety data needed to
design a tenofovir regimen that can be used in trials to evaluate the
efficacy of tenofovir in prevention of mother to child HIV transmission.
Protocol Status:
Enrolling
Study
Summary
Study Purpose: To evaluate the safety and pharmacokinetics of tenofovir disoproxil fumarate (TDF) when administered to HIV infected pregnant women during labor and to their infants during the first week of life to determine the optimal regimen for a subsequent efficacy trial, if indicated.
Study Design: Phase I, open label, non-controlled trial with three mother/infant cohorts - cohort 1: drug only to mother; cohort 2: drug only to infant and cohort 3: drug to both mothers and infants. Cohort 3 will be enrolled after participants in the first two have completed at least 6 weeks of follow-up and the safety and pk data have been evaluated.
Study Population: Mothers: HIV-1 infected pregnant women; Infants: born to HIV-1 infected enrolled mothers.
Study Size: 80 mother/infant pairs, 30 in cohorts 1 and 3 and 20 in cohort 2.
Study Duration: Total duration of the study will be approximately 2 years. Participants will be enrolled in one of the three cohorts over a period of approximately 6-9 months. Mothers and infants will be followed through 12 months postpartum.
Treatment Regimen: Eligible women and their infants will be enrolled in one of three cohorts. Cohort 1: Mothers will receive a single 600 mg oral dose of TDF at onset of labor; infants will not be dosed. Cohort 2: Mothers will not be dosed; infants will receive 4 mg/kg of the TDF oral suspension at birth (within 12 hours) and on Days 3 and 5 of life. Cohort 3: Mothers will receive a single 600 mg oral dose of TDF at onset of labor and infants will receive 4 mg/kg of the TDF oral suspension at birth (within 12 hours) and on Days 3 and 5 of life.
Primary Objectives: To evaluate the safety and tolerance of intrapartum/neonatal TDF in HIV-infected women and their infants.
To evaluate the pharmacokinetics of intrapartum/neonatal TDF in HIV-infected women and their infants and to determine maternal plasma exposure with single doses of 600 mg and, if necessary, 900 mg.
Secondary Objectives: To evaluate the effect of a single dose of TDF on maternal HIV-1 RNA levels, and to determine if there is RNA rebound above baseline following washout of the drug in study participants, at 5 to 7 days and 6 weeks postpartum.
To evaluate viral resistance to TDF at 5 to 7 days and 6 weeks post partum in women following single intrapartum dosing, and if detected, to determine the duration of expression.
To evaluate viral resistance to TDF in viral isolates from HIV-infected infants.
To determine the infection status of participating infants.
To measure TDF concentration in amniotic fluid and breastmilk following maternal exposure to intrapartum TDF.
SDMC Protocol Specialist:
Lynda Marie Emel
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Protocol Co-Chair:
George Kafulafula
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Protocol Co-Chair:
Regis Kreitchmann
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Protocol Chair:
Mark Mirochnick
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DAIDS Medical Officer:
Sheryl Zwerski
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CORE Protocol Specialist:
Kathy George
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