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

NCT00120471 | Completed Phase 1

• 2 other identifiers: HPTN 05710143
• Study Type: interventional
• Target: 122
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

HIV Infections

Keywords

Perinatal Transmission; MTCT; HIV Seronegativity

Outcome Measures

Primary Outcomes (2)

• Frequency of adverse events with a severity of Grade 3 or higher attributable to receipt of TDF

  Throughout study

• Maintenance of infant serum concentrations of TDF greater than 50 ng/ml

  Through Week 1

Secondary Outcomes (4)

• Maternal HIV-1 RNA levels

  At study entry, Days 5 to 7, and Week 6

• Viral resistance to TDF in all HIV-1 infected infants, all of the corresponding mothers (transmitters), and a subset of mothers whose infants are not infected (nontransmitters). Analysis of TDF in mothers may include testing of breastmilk samples.

  Throughout study

• HIV infection in infants

  Throughout study

• TDF concentration in amniotic fluid and breast milk

  Through Week 1

Study Arms (4)

1

EXPERIMENTAL

Pregnant participants will receive a single dose of TDF during active labor. These participants will be hospitalized at the delivery facility through Day 3 postpartum.

Drug: Tenofovir disoproxil fumarate

2

EXPERIMENTAL

Pregnant participants will not receive TDF. Participants 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.

Drug: Tenofovir disoproxil fumarate

3

EXPERIMENTAL

Pregnant participants will be hospitalized at the delivery facility through Day 7 postpartum. They will receive TDF during active labor and their infants will receive TDF at birth and on Days 3 and 5 after birth.

Drug: Tenofovir disoproxil fumarate

4

EXPERIMENTAL

Pregnant participants will be hospitalized at the delivery facility through Day 7 postpartum. Mothers will receive TDF during active labor and their infants will receive TDF at birth and daily for 7 days after birth.

Drug: Tenofovir disoproxil fumarate

Interventions

Tenofovir disoproxil fumarate DRUG

600-mg tablet taken orally once daily

Also known as: TDF

1; 3; 4

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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.)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute on Drug Abuse (NIDA): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (5)

Federal Univ. of Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

Location

Hospital Nossa Senhora da Conceicao CRS

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Irmandade Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Location

HSE-Hospital dos Servidores do Estado CRS

Rio de Janeiro, 20221-903, Brazil

Location

College of Med. JHU CRS

Blantyre, Malawi

Location

Related 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.

  PMID: 15595430 BACKGROUND

• 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.

  PMID: 15701581 BACKGROUND

• 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.

  PMID: 15049430 BACKGROUND

• 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.

  PMID: 12616665 BACKGROUND

• Osorio LE, Boechat MI, Mirochnick M, Kumwenda N, Kreitchmann R, Emel L, Pinto J, Joao E, Santos B, Swenson M, George K, Sato P, Mofenson L, Nielsen-Saines K; HIV Prevention Trials Network (HPTN) 057 Protocol Team. Bone Age and Mineral Density Assessments Using Plain Roentgenograms in Tenofovir-exposed Infants in Malawi and Brazil Enrolled in HIV Prevention Trials Network 057. Pediatr Infect Dis J. 2017 Feb;36(2):184-188. doi: 10.1097/INF.0000000000001386.

  PMID: 27798550 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

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; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mark Mirochnick, MD

  Boston Medical Center

  STUDY CHAIR

• Taha Taha, MD, PhD

  Johns Hopkins University

  STUDY CHAIR

• Regis Kreitchmann, MD

  Centro Municipal de DST/AIDS, Irmandade Santa Casa de Misericordia de Porto Alegre

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: July 14, 2005
• First Posted: July 18, 2005
• Study Start: November 1, 2006
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

BR (4); MA (1)