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

NCT00076791 | Completed Phase 1

• 4 other identifiers: P39410034PACTG 394IMPAACT 394
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 12

Brief Summary

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.

Conditions

HIV Infections

Keywords

HIV Seronegativity

Outcome Measures

Primary Outcomes (1)

• Adverse experiences with a severity of Grade 3 or 4 and adverse pregnancy outcomes that cannot be directly attributed to a cause besides study treatment

  Throughout study

Secondary Outcomes (3)

• Maternal viral load

  during active labor and 24 to 48 hours, 7 days, 6 to 8 weeks, and 12 weeks postpartum

• viral resistance to emtricitabine/tenofovir disoproxil fumarate using bulk sequencing

  at Weeks 1, 6, and 12 postpartum

• infant HIV DNA PCR

  at 24 to 48 hours, 6 to 8 weeks, 4 months, and 6 months of life

Study Arms (2)

1

ACTIVE COMPARATOR

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.

Drug: Emtricitabine/Tenofovir disoproxil fumarate; Drug: Tenofovir disoproxil fumarate

2

ACTIVE COMPARATOR

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.

Drug: Emtricitabine/Tenofovir disoproxil fumarate; Drug: Tenofovir disoproxil fumarate

Interventions

Emtricitabine/Tenofovir disoproxil fumarate DRUG

900 mg of TDF combined with 600 mg emtricitabine

1; 2

Tenofovir disoproxil fumarate DRUG

600 mg oral dose of TDF

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV infected
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: collaborator

Study Sites (12)

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

Washington D.C., District of Columbia, 20010, United States

Location

Washington Hosp. Ctr. NICHD CRS

Washington D.C., District of Columbia, 20010, United States

Location

Univ. of Miami Ped. Perinatal HIV/AIDS CRS

Miami, Florida, 33136, United States

Location

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

Chicago, Illinois, 60608, United States

Location

Children's Hospital of Michigan NICHD CRS

Detroit, Michigan, 48201, United States

Location

NJ Med. School CRS

Newark, New Jersey, 07101-1709, United States

Location

Nyu Ny Nichd Crs

New York, New York, 10016, United States

Location

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, 10457, United States

Location

Hahnemann Univ. Hosp.

Philadelphia, Pennsylvania, 19102-1192, United States

Location

Regional Med. Ctr. at Memphis

Memphis, Tennessee, United States

Location

St. Jude/UTHSC CRS

Memphis, Tennessee, United States

Location

San Juan City Hosp. PR NICHD CRS

San Juan, Puerto Rico

Location

Related Publications (5)

• 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.

  PMID: 12523458 BACKGROUND

• 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.

  PMID: 12943497 BACKGROUND

• 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.

  PMID: 15778108 BACKGROUND

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

  PMID: 15595430 BACKGROUND

• 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.

  PMID: 15794723 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Patricia M. Flynn, MD

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

  STUDY CHAIR

• Arlene D. Bardeguez, MD, MPH, FACOG

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2004
• First Posted: February 6, 2004
• Study Start: March 1, 2004
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2011
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (11); PR (1)