Safety of Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine/TDF in HIV Infected Pregnant Women and Their Infants

NCT ID: NCT00076791

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-03-31

Study Completion Date

2011-03-31

Brief Summary

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Most infants infected with HIV through mother-to-child transmission (MTCT, or perinatal transmission) become infected during labor and delivery. The purpose of this study is to test the safety and tolerability of a single dose of tenofovir disoproxil fumarate (TDF) or emtricitabine/TDF (FTC/TDF) given at the time of labor to HIV infected pregnant women and to their newborn infants.

Detailed Description

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The majority of perinatally infected infants are infected during the labor and delivery process, but recent studies suggest that additional factors, such as postexposure prophylaxis, are likely to be involved in the prevention of MTCT of HIV. It is possible that antiretroviral dosing only during labor and short-term dosing to newly born infants would be sufficiently effective to prevent MTCT of HIV. TDF is a nucleoside reverse transcriptase inhibitor that has demonstrated significant effectiveness in preventing MTCT of simian immunodeficiency virus (SIV) in a primate model of HIV. FTC/TDF is a combination of two NRTIs being studied because this combination has the potential to prevent MTCT, while protecting the mother from developing resistance that may develop with single drug therapy. This study will evaluate the safety, tolerance, and pharmacokinetics (PK) of single doses of TDF and FTC/TDF in both HIV infected pregnant women and their newborn infants.

Cohort 1 is now closed. Each participant in Cohort 1 received a single 600 mg oral dose of TDF at the start of active labor or 4 hours prior to C-section, with concurrent administration of standard intravenous zidovudine (ZDV) prophylaxis and/or other antiretrovirals prescribed by her physician. The infants from Cohort 1 received only the standard 6 weeks of oral ZDV prophylaxis postpartum. PK blood samples were taken from mothers at predose and 1, 2, 4, 8, 12, and 24 hours postdose and at the time of delivery; PK blood samples were taken from infants at 12, 24, and 36 hours after birth.

Pregnant women with HIV infection entering this study will be assigned to Cohort 2, as all infants in Cohort 1 have completed the 6 to 8 week study visit and all Cohort 1 data have been reviewed. Mothers in Cohort 2 will receive a single dose of 900 mg of TDF combined with 600 mg emtricitabine, along with standard ZDV prophylaxis and/or other antiretrovirals prescribed by her physician. Infants will receive a single dose of TDF at 4 mg/kg combined with 3 mg/kg emtricitabine as soon as possible after delivery and within 6 hours of age as well as the standard 6 weeks of oral ZDV prophylaxis after birth. Blood samples from mothers and infants will be taken as for Cohort 1.

Mothers will be followed for 12 weeks postpartum or for 2 years after giving birth if viral resistance to TDF or FTC/TDF is demonstrated at Weeks 1, 6, or 12. In addition to the PK studies, blood collection will occur around the time of delivery, at screening, study entry, at delivery, and after delivery at various times up to Week 12. Physical exams will be done at screening, study entry, at delivery, and after delivery at various times up to Week 8. Infants will be followed until age 2. Blood will be collected and physical exams will be done at birth and at various times up to Week 96. Mothers are encouraged to coenroll in PACTG P1025, Pharmacokinetic Study of Anti-HIV Drugs During Pregnancy.

Conditions

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HIV Infections

Keywords

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HIV Seronegativity

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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1

Each participant in Cohort 1 received a single 600 mg oral dose of TDF at the start of active labor or 4 hours prior to C-section, with concurrent administration of standard intravenous zidovudine (ZDV) prophylaxis and/or other antiretrovirals prescribed by her physician. The infants from Cohort 1 received only the standard 6 weeks of oral ZDV prophylaxis postpartum.

Group Type ACTIVE_COMPARATOR

Emtricitabine/Tenofovir disoproxil fumarate

Intervention Type DRUG

900 mg of TDF combined with 600 mg emtricitabine

Tenofovir disoproxil fumarate

Intervention Type DRUG

600 mg oral dose of TDF

2

Mothers in Cohort 2 will receive a single dose of 900 mg of TDF combined with 600 mg emtricitabine, along with standard ZDV prophylaxis and/or other antiretrovirals prescribed by her physician. Infants will receive a single dose of TDF at 4 mg/kg combined with 3 mg/kg emtricitabine as soon as possible after delivery and within 6 hours of age as well as the standard 6 weeks of oral ZDV prophylaxis after birth.

Group Type ACTIVE_COMPARATOR

Emtricitabine/Tenofovir disoproxil fumarate

Intervention Type DRUG

900 mg of TDF combined with 600 mg emtricitabine

Tenofovir disoproxil fumarate

Intervention Type DRUG

600 mg oral dose of TDF

Interventions

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Emtricitabine/Tenofovir disoproxil fumarate

900 mg of TDF combined with 600 mg emtricitabine

Intervention Type DRUG

Tenofovir disoproxil fumarate

600 mg oral dose of TDF

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV infected
* 34 weeks or more (third trimester) into pregnancy at study screening
* Have access to a participating AIDS clinical trial unit (ACTU) and are willing to be followed at location for the duration of the study

Exclusion Criteria

* Prior treatment with TDF, including coformulated drugs that contain TDF, during current pregnancy
* Active opportunistic infection and/or serious bacterial infection at time of study entry
* Certain abnormal laboratory values at study screening
* Chronic malabsorption or chronic diarrhea
* Certain medical or obstetrical complications during the current pregnancy
* Fetal abnormalities as measured by ultrasound screening performed at 18 weeks into pregnancy or later
* Intend to breastfeed
* Current alcohol abuse or use of illicit substances
* Participation in any other therapeutic or vaccine perinatal treatment trial during the current pregnancy, unless given permission by the protocol chairs
* Require certain medications
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patricia M. Flynn, MD

Role: STUDY_CHAIR

Department of Infectious Disease, St. Jude's Children's Research Hospital

Arlene D. Bardeguez, MD, MPH, FACOG

Role: STUDY_CHAIR

Obstetrics, Gynecology, and Women's Health, University of Medicine and Dentistry of New Jersey

Locations

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Children's National Med. Ctr. Washington DC NICHD CRS

Washington D.C., District of Columbia, United States

Site Status

Washington Hosp. Ctr. NICHD CRS

Washington D.C., District of Columbia, United States

Site Status

Univ. of Miami Ped. Perinatal HIV/AIDS CRS

Miami, Florida, United States

Site Status

Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program

Chicago, Illinois, United States

Site Status

Children's Hospital of Michigan NICHD CRS

Detroit, Michigan, United States

Site Status

NJ Med. School CRS

Newark, New Jersey, United States

Site Status

Nyu Ny Nichd Crs

New York, New York, United States

Site Status

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, United States

Site Status

Hahnemann Univ. Hosp.

Philadelphia, Pennsylvania, United States

Site Status

Regional Med. Ctr. at Memphis

Memphis, Tennessee, United States

Site Status

St. Jude/UTHSC CRS

Memphis, Tennessee, United States

Site Status

San Juan City Hosp. PR NICHD CRS

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Antoniou T, Park-Wyllie LY, Tseng AL. Tenofovir: a nucleotide analog for the management of human immunodeficiency virus infection. Pharmacotherapy. 2003 Jan;23(1):29-43. doi: 10.1592/phco.23.1.29.31915.

Reference Type BACKGROUND
PMID: 12523458 (View on PubMed)

Kourtis AP, Duerr A. Prevention of perinatal HIV transmission: a review of novel strategies. Expert Opin Investig Drugs. 2003 Sep;12(9):1535-44. doi: 10.1517/13543784.12.9.1535.

Reference Type BACKGROUND
PMID: 12943497 (View on PubMed)

Moodley J, Moodley D. Management of human immunodeficiency virus infection in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2005 Apr;19(2):169-83. doi: 10.1016/j.bpobgyn.2004.10.007. Epub 2004 Dec 15.

Reference Type BACKGROUND
PMID: 15778108 (View on PubMed)

Abrams EJ. Prevention of mother-to-child transmission of HIV--successes, controversies and critical questions. AIDS Rev. 2004 Jul-Sep;6(3):131-43.

Reference Type BACKGROUND
PMID: 15595430 (View on PubMed)

Thorne C, Newell ML. The safety of antiretroviral drugs in pregnancy. Expert Opin Drug Saf. 2005 Mar;4(2):323-35. doi: 10.1517/14740338.4.2.323.

Reference Type BACKGROUND
PMID: 15794723 (View on PubMed)

Other Identifiers

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10034

Identifier Type: REGISTRY

Identifier Source: secondary_id

PACTG 394

Identifier Type: -

Identifier Source: secondary_id

IMPAACT 394

Identifier Type: -

Identifier Source: secondary_id

P394

Identifier Type: -

Identifier Source: org_study_id