Safety of Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine/TDF in HIV Infected Pregnant Women and Their Infants
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| ClinicalTrials.gov Identifier: NCT00076791 |
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Recruitment Status
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Completed
First Posted
: February 6, 2004
Last Update Posted
: July 9, 2013
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infections | Drug: Emtricitabine/Tenofovir disoproxil fumarate Drug: Tenofovir disoproxil fumarate | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 66 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| 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 Start Date : | March 2004 |
| Actual Primary Completion Date : | March 2010 |
| Actual Study Completion Date : | March 2011 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 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.
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Drug: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Drug: Tenofovir disoproxil fumarate
600 mg oral dose of TDF
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Active Comparator: 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.
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Drug: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Drug: Tenofovir disoproxil fumarate
600 mg oral dose of TDF
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- 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 [ Time Frame: Throughout study ]
- Maternal viral load [ Time Frame: 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 [ Time Frame: at Weeks 1, 6, and 12 postpartum ]
- infant HIV DNA PCR [ Time Frame: at 24 to 48 hours, 6 to 8 weeks, 4 months, and 6 months of life ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00076791
| United States, District of Columbia | |
| Children's National Med. Ctr. Washington DC NICHD CRS | |
| Washington, District of Columbia, United States, 20010 | |
| Washington Hosp. Ctr. NICHD CRS | |
| Washington, District of Columbia, United States, 20010 | |
| United States, Florida | |
| Univ. of Miami Ped. Perinatal HIV/AIDS CRS | |
| Miami, Florida, United States, 33136 | |
| United States, Illinois | |
| Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program | |
| Chicago, Illinois, United States, 60608 | |
| United States, Michigan | |
| Children's Hospital of Michigan NICHD CRS | |
| Detroit, Michigan, United States, 48201 | |
| United States, New Jersey | |
| NJ Med. School CRS | |
| Newark, New Jersey, United States, 07101-1709 | |
| United States, New York | |
| Bronx-Lebanon Hosp. IMPAACT CRS | |
| Bronx, New York, United States, 10457 | |
| Nyu Ny Nichd Crs | |
| New York, New York, United States, 10016 | |
| United States, Pennsylvania | |
| Hahnemann Univ. Hosp. | |
| Philadelphia, Pennsylvania, United States, 19102-1192 | |
| United States, Tennessee | |
| Regional Med. Ctr. at Memphis | |
| Memphis, Tennessee, United States | |
| St. Jude/UTHSC CRS | |
| Memphis, Tennessee, United States | |
| Puerto Rico | |
| San Juan City Hosp. PR NICHD CRS | |
| San Juan, Puerto Rico | |
| Study Chair: | 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 |
Publications:
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00076791 History of Changes |
| Other Study ID Numbers: |
P394 10034 ( Registry Identifier: DAIDS ES ) PACTG 394 IMPAACT 394 |
| First Posted: | February 6, 2004 Key Record Dates |
| Last Update Posted: | July 9, 2013 |
| Last Verified: | July 2013 |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
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HIV Seronegativity |
Additional relevant MeSH terms:
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HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Tenofovir |
Emtricitabine Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents |