Safety and Blood Levels of Tenofovir Disoproxil Fumarate in HIV Infected Pregnant Women and Their Babies

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

122 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-30

Study Completion Date

2011-12-31

Brief Summary

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To prevent mother-to-child transmission (MTCT) of HIV in resource-limited countries, a simple yet effective treatment plan is needed. Tenofovir disoproxil fumarate (TDF) is an anti-HIV drug approved for use in the United States for the treatment of HIV infected adults. The purpose of this study is to determine the safety, tolerability, and blood levels of TDF in HIV infected pregnant women and their babies. The study will be conducted at sites in Malawi and Brazil.

Detailed Description

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Rates of MTCT of HIV have dramatically decreased in resource-rich countries since the introduction of antiretroviral (ARV) prophylaxis; increased prenatal care, HIV testing, and counseling; elective cesarean delivery; and avoidance of breastfeeding. In resource-limited countries, however, MTCT of HIV continues to be a widespread problem. In these parts of the world, ARV prophylaxis is too expensive and too difficult to adequately administer; mothers often do not receive proper prenatal care; cesarean delivery may pose risks to the mother and and her infant; and due to the lack of safe, affordable, and socially acceptable alternatives, HIV infected mothers breastfeed their infants. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of TDF in HIV infected pregnant women and their infants.

Participants in this study will be enrolled through 12 months after delivery. During the last trimester of pregnancy, HIV infected women will be screened for eligibility. Women will be enrolled into the study upon presentation at the study site for delivery. Standard of care with ARVs for prevention of MTCT will be offered to all women and their infants both inside and outside of the study; however, such ARVs will not be provided by this study.

There will be four cohorts in this study:

* Cohort 1 women will receive a single dose of TDF (SD TDF) during active labor. Cohort 1 women will be hospitalized at the delivery facility through Day 3 postpartum.
* Cohort 2 women will not receive any TDF. Cohort 2 women will be hospitalized at the delivery facility through Day 7 postpartum. Their infants will receive TDF at birth and on Days 3 and 5 after birth.
* Cohort 3 will not begin enrolling women until data safety evaluations of Cohorts 1 and 2 are completed. Cohort 3 women will be hospitalized at the delivery facility through Day 7 postpartum. Women in Cohort 3 will receive SD TDF during active labor, and their infants will receive TDF at birth and on Days 3 and 5 after birth.
* Cohort 4, which was added to the study based on a review of data from the other cohorts, will be similar to Cohort 3, except that infants will receive daily TDF for the 7 days after birth. Researchers believe this higher and more frequent dosing of TDF in infants will help them meet the target TDF concentration specified in the protocol.

There will be seven study visits for women at study entry (Day 0), Day 2, between Days 5 and 7, at Weeks 6 and 12, and at Months 6 and 12 postpartum. Medical history, a short physical exam, and blood collection will occur at all visits. In Cohorts 1, 3, and 4, blood collection for PK studies will occur prior to receiving TDF and seven times post-dose.

There will be eight study visits for infants, which will occur within 24 hours of birth; on Day 3; between Days 5 and 7; at Weeks 6 and 12; and at Months 6, 9, and 12. Medical history, a physical exam, and blood collection will occur at all visits. Infants will have x-rays to assess bone health at Day 3 and Month 3, except in Cohort 4, which will not include x-rays of infants. Infants of Cohort 1 will have blood collection for PK studies at birth and four times after birth. Infants of Cohorts 2 and 3 will undergo blood collections for PK studies at birth, Day 3, and Day 5. Blood collection at these visits will occur before receiving TDF and 2 and 10 hours after receiving TDF. At birth, an additional collection will occur 18 to 24 hours after receiving TDF, and on Day 5, two additional collections will occur--at 18 to 24 hours and at 36 to 48 hours after receiving TDF. Infants of Cohort 4 will have blood collection for PK studies at birth and after their fourth and seventh doses of TDF.

Conditions

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HIV Infections

Keywords

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Perinatal Transmission MTCT HIV Seronegativity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Intervention Type DRUG

6-mg/kg oral suspension taken at birth and daily for 7 days after birth

Interventions

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Tenofovir disoproxil fumarate

600-mg tablet taken orally once daily

Intervention Type DRUG

Tenofovir disoproxil fumarate

4-mg/kg oral suspension taken at birth and on Days 3 and 5 after birth

Intervention Type DRUG

Tenofovir disoproxil fumarate

6-mg/kg oral suspension taken at birth and daily for 7 days after birth

Intervention Type DRUG

Other Intervention Names

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TDF TDF TDF

Eligibility Criteria

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Inclusion Criteria

* HIV-1 infected
* Intend to deliver at the study site
* Willing to be contacted or visited at home
* Willing to be admitted to and remain in the delivery facility through Day 3 postpartum (Cohort 1) or Day 7 postpartum (Cohorts 2 and 3)

Exclusion Criteria

* Prior treatment with TDF
* Active opportunistic infection
* Serious bacterial infection
* Chronic malabsorption or diarrhea during the current pregnancy
* Clinically significant disease or condition that, in the opinion of the study clinician, would interfere with the study
* Known multiple gestation (twins, etc.) prior to study entry
* Participation in any other therapeutic or vaccine trial during the current pregnancy
* Use of certain medications
* Any other condition or situation that, in the opinion of the investigator, would interfere with the study
* For Cohort 4, use of atazanavir or lopinavir/ritonavir (Kaletra) within 2 weeks of anticipated delivery

* Birth weight of less than 2 kg (4.4 lbs)
* Severe congenital malformation or other medical condition that may affect survival and, in the opinion of the clinician, participation in this study
* Grade 2 or higher serum creatinine level or any other Grade 3 or higher toxicity
* Part of a multiple birth (twins, etc.)

Minimum Eligible Age

18 Years

Review the countries where the study has at least one active or historical site.

Brazil Malawi

Review additional registry numbers or institutional identifiers associated with this trial.

10143

Identifier Type: REGISTRY

Identifier Source: secondary_id

HPTN 057

Identifier Type: -

Identifier Source: org_study_id

Safety and Blood Levels of Tenofovir Disoproxil Fumarate in HIV Infected Pregnant Women and Their Babies

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

1

Tenofovir disoproxil fumarate

2

Tenofovir disoproxil fumarate

3

Tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate

4

Tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate

Interventions

Tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate

Other Intervention Names

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

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

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party

Principal Investigators

Mark Mirochnick, MD

Taha Taha, MD, PhD

Regis Kreitchmann, MD

Locations

Federal Univ. of Minas Gerais

Hospital Nossa Senhora da Conceicao CRS

Irmandade Santa Casa de Misericórdia de Porto Alegre

HSE-Hospital dos Servidores do Estado CRS

College of Med. JHU CRS

Countries

References

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

Capparelli E, Rakhmanina N, Mirochnick M. Pharmacotherapy of perinatal HIV. Semin Fetal Neonatal Med. 2005 Apr;10(2):161-75. doi: 10.1016/j.siny.2004.10.001. Epub 2005 Jan 20.

Thorne C, Newell ML. Mother-to-child transmission of HIV infection and its prevention. Curr HIV Res. 2003 Oct;1(4):447-62. doi: 10.2174/1570162033485140.

Capparelli EV, Englund JA, Connor JD, Spector SA, McKinney RE, Palumbo P, Baker CJ. Population pharmacokinetics and pharmacodynamics of zidovudine in HIV-infected infants and children. J Clin Pharmacol. 2003 Feb;43(2):133-40. doi: 10.1177/0091270002239821.

Other Identifiers

10143

HPTN 057