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

Study Summary
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What was HPTN 057?

A Phase I, open label, non-controlled trial 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.

Who participated in the study?

Mothers: HIV-1 infected pregnant women; Infants: born to HIV-1 infected enrolled mothers (110 fully evaluable mother/infant pairs)

What happened during the study?

Eligible women and their infants were enrolled in one of four cohorts:

Cohort 1: Mothers received a single 600 mg oral dose of TDF at onset of labor; infants were not dosed.

Cohort 2: Mothers were not dosed; infants receivde 4 mg/kg of the TDF oral suspension at birth (within 12 hours) and on Days 3 and 5 of life.

Cohort 3: Mothers received a single 900 mg oral dose of TDF at onset of labor and infants received 6 mg/kg of the TDF oral suspension at birth (within 12 hours) and on Days 3 and 5 of life.

Cohort 4: Mothers received a single 600 mg oral dose of TDF at onset of labor and infants received 6 mg/kg of the TDF oral suspension daily for 7 days initiated at birth.

Why was this study important?

HPTN 057 provided 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

Study Documents

Study Details

Protocol Status: Concluded
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.
Eligible women and their infants will be enrolled in one of four cohorts outlined below. Irrespective of and outside of this Phase I study of TDF, all participating women and infants will be offered the local standard of care antiretroviral regimen for prevention of mother to child HIV transmission. Cohort 4 was added after reviewing the pharmacokinetic and safety data from Cohorts 1 and 3.

Study Population:

Mothers: HIV-1 infected pregnant women; Infants: born to HIV-1 infected enrolled mothers.

Study Size:

110 fully evaluable mother/infant pairs

Study Duration:

The duration of Cohorts 1 - 3 will be approximately two years. Enrollment is expected to take approximately 6-9 months, with enrollment of Cohort 3 beginning after all mothers and infants in Cohort 1 and 2 have been followed for a minimum 6 weeks postpartum. Cohort 4 will begin after Cohorts 1 - 3 have completed follow-up and is expected to take approximately 6 months. Mothers and infants in all four cohorts will be followed through 12 months post delivery.

Treatment Regimen:

Eligible women and their infants will be enrolled in one of four 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 900 mg oral dose of TDF at onset of labor and infants will receive 6 mg/kg of the TDF oral suspension at birth (within 12 hours) and on Days 3 and 5 of life.

Cohort 4 mothers will receive a single 600 mg oral dose of TDF at onset of labor and infants will receive 6 mg/kg of the TDF oral suspension daily for 7 days initiated at birth.

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 in HIV isolates from maternal plasma, infant plasma, and breastmilk.
To determine the infection status of participating infants.
To measure TDF concentration in amniotic fluid and breastmilk following maternal exposure to intrapartum TDF.

Key Study Personnel

Lynda Marie Emel, SDMC Protocol Specialist
Kathleen George, CORE Protocol Specialist
Regis Kreitchmann, Protocol Co-Chair
Mark Mirochnick, Protocol Chair
Paul Sato, DAIDS Medical Officer
Taha Taha, Protocol Co-Chair