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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00076791
• Other study ID #: P394
• Secondary ID: 10034PACTG 394IM
• Status: Completed
• Phase: Phase 1
• Start date: March 2004
• Est. completion date: March 2011

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: March 2011
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
• Tenofovir disoproxil fumarate
600 mg oral dose of TDF

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
United States	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York
United States	Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program	Chicago	Illinois
United States	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan
United States	Regional Med. Ctr. at Memphis	Memphis	Tennessee
United States	St. Jude/UTHSC CRS	Memphis	Tennessee
United States	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida
United States	Nyu Ny Nichd Crs	New York	New York
United States	NJ Med. School CRS	Newark	New Jersey
United States	Hahnemann Univ. Hosp.	Philadelphia	Pennsylvania
United States	Children's National Med. Ctr. Washington DC NICHD CRS	Washington	District of Columbia
United States	Washington Hosp. Ctr. NICHD CRS	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Thorne C, Newell ML. The safety of antiretroviral drugs in pregnancy. Expert Opin Drug Saf. 2005 Mar;4(2):323-35. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Maternal viral load		during active labor and 24 to 48 hours, 7 days, 6 to 8 weeks, and 12 weeks postpartum
Secondary	viral resistance to emtricitabine/tenofovir disoproxil fumarate using bulk sequencing		at Weeks 1, 6, and 12 postpartum
Secondary	infant HIV DNA PCR		at 24 to 48 hours, 6 to 8 weeks, 4 months, and 6 months of life

External Links

•   Click here for more information on after birth care for HIV positive women and their babies
•   Click here for more information on HIV and pregnancy
•   Click here for more information on medication regimens for HIV positive pregnant women