Safety of Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine/TDF in HIV Infected Pregnant Women and Their Infants
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Emtricitabine/Tenofovir disoproxil fumarate (Drug); Tenofovir disoproxil fumarate (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Patricia M. Flynn, MD, Study Chair, Affiliation: Department of Infectious Disease, St. Jude's Children's Research Hospital Arlene D. Bardeguez, MD, MPH, FACOG, Study Chair, Affiliation: Obstetrics, Gynecology, and Women's Health, University of Medicine and Dentistry of New Jersey
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.
Clinical Details
Official title: A Phase I Study of the Safety, Tolerance, and Pharmacokinetics of Tenofovir Disoproxil Fumarate (TDF) and the Combination of TDF Plus Emtricitabine in HIV-1 Infected Pregnant Women and Their Infants
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: 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
Secondary outcome: Maternal viral loadviral resistance to emtricitabine/tenofovir disoproxil fumarate using bulk sequencing infant HIV DNA PCR
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria for Mothers:
- 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 for Mothers:
- 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
Locations and Contacts
San Juan City Hosp. PR NICHD CRS, San Juan, Puerto Rico
Children's National Med. Ctr. Washington DC NICHD CRS, Washington, District of Columbia 20010, United States
Washington Hosp. Ctr. NICHD CRS, Washington, District of Columbia 20010, United States
Univ. of Miami Ped. Perinatal HIV/AIDS CRS, Miami, Florida 33136, United States
Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program, Chicago, Illinois 60608, United States
Children's Hospital of Michigan NICHD CRS, Detroit, Michigan 48201, United States
NJ Med. School CRS, Newark, New Jersey 07101-1709, United States
Bronx-Lebanon Hosp. IMPAACT CRS, Bronx, New York 10457, United States
Nyu Ny Nichd Crs, New York, New York 10016, United States
Hahnemann Univ. Hosp., Philadelphia, Pennsylvania 19102-1192, United States
Regional Med. Ctr. at Memphis, Memphis, Tennessee, United States
St. Jude/UTHSC CRS, Memphis, Tennessee, United States
Additional Information
Click here for more information about emtricitabine/tenofovir disoproxil fumarate Click here for more information about tenofovir disoproxil fumarate Click here for more information on HIV and pregnancy Click here for more information on medication regimens for HIV positive pregnant women Click here for more information on after birth care for HIV positive women and their babies
Related publications: 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. Review. Kourtis AP, Duerr A. Prevention of perinatal HIV transmission: a review of novel strategies. Expert Opin Investig Drugs. 2003 Sep;12(9):1535-44. Review. Moodley J, Moodley D. Management of human immunodeficiency virus infection in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2005 Apr;19(2):169-83. Epub 2004 Dec 15. Review. Abrams EJ. Prevention of mother-to-child transmission of HIV--successes, controversies and critical questions. AIDS Rev. 2004 Jul-Sep;6(3):131-43. Review. Thorne C, Newell ML. The safety of antiretroviral drugs in pregnancy. Expert Opin Drug Saf. 2005 Mar;4(2):323-35. Review.
Starting date: March 2004
Last updated: July 5, 2013
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