Safety Study of a Tenofovir-containing Drug Regimen for the Prevention of Mother-to-child Transmission of HIV and HBV (TiP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by Centers for Disease Control and Prevention
Sponsor:
Collaborator:
National Center for AIDS/STD Control and Prevention, China CDC
Information provided by (Responsible Party):
Athena Kourtis, Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01125696
First received: March 29, 2010
Last updated: February 3, 2014
Last verified: June 2012
  Purpose

The purpose of this study is to compare a regimen of tenofovir/lamivudine/lopinavir-ritonavir to the WHO-recommended and locally practiced standard of care regimen consisting of zidovudine/lamivudine/lopinavir-ritonavir during the second and third trimesters of pregnancy in HIV and HBV co-infected women. This is a phase II study evaluating the safety of the test regimen in pregnant women and their newborns. While the study is not powered to examine efficacy, preliminary estimates of transmission of HIV and HBV to the infants and of the rate of resistance development will be obtained.


Condition Intervention Phase
HIV
Hepatitis B
Drug: Tenofovir/lamivudine/lopinavir-ritonavir
Drug: Zidovudine/lamivudine/lopinavir-ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Maternal Tenofovir-containing Combination Drug Regimen During the Second and Third Trimesters of Pregnancy for Prevention of Mother-to-child Transmission of HIV and HBV in HIV-HBV Co-infected Mothers

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Tenofovir Safety for mothers measured by incidence of serious adverse events (SAEs) [ Time Frame: From baseline (14-28 weeks gestation) through 12 months postpartum ] [ Designated as safety issue: Yes ]
    SAEs will be defined using the DAIDS Toxicity Tables

  • Dual Energy X-ray absorptiometry (DXA) scans of bone mineral density [ Time Frame: from delivery through 6 months postpartum ] [ Designated as safety issue: Yes ]
    Mothers will have DXA scan of hip and lumbar spine. Infants will have DXA scan of whole body and lumbar spine.

  • Maternal Tenofovir Pharmacokinetics [ Time Frame: 16 weeks gestation through delivery ] [ Designated as safety issue: Yes ]
    Only for mothers on the active arm.

  • Infant Tenofovir Pharmacokinetics [ Time Frame: one timepoint within 12 hours of delivery ] [ Designated as safety issue: Yes ]
    Only for infants on the active arm.

  • Tenofovir safety for infants measured by incidence of serious adverse events (SAEs) [ Time Frame: from birth through 12 months of age ] [ Designated as safety issue: Yes ]
    SAEs defined according to the DAIDS toxicity tables.


Secondary Outcome Measures:
  • HBV viral load in mothers [ Time Frame: from baseline (14-28 weeks gestation) through delivery ] [ Designated as safety issue: No ]
  • Infant HIV transmission rate [ Time Frame: birth through 12 months ] [ Designated as safety issue: No ]
  • Infant HBV transmission rate [ Time Frame: birth through 12 months ] [ Designated as safety issue: No ]
  • Prevalence of HIV resistance mutations [ Time Frame: from baseline (14-28 weeks gestation) through 12 months postpartum ] [ Designated as safety issue: No ]
  • Prevalence of HBV resistance mutations [ Time Frame: from baseline (14-28 weeks gestation) through 12 months postpartum ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: May 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard of Care Drug: Zidovudine/lamivudine/lopinavir-ritonavir
Zidovudine/lamivudine/lopinavir-ritonavir given to mothers starting at 14-28 weeks gestation till labor/delivery and continued postpartum if maternal baseline CD4<350
Experimental: Tenofovir Drug: Tenofovir/lamivudine/lopinavir-ritonavir
Tenofovir/lamivudine/lopinavir-ritonavir given to mothers starting at 14-28 weeks gestation till labor/delivery and continued postpartum if maternal baseline CD4<350

Detailed Description:

Great progress has been made in preventing mother-to-child transmission (MTCT) of HIV in resource-rich settings with the use of combination antiretroviral regimens during pregnancy and peripartum. In the resource-limited world simple inexpensive regimens administered peripartum, such as single dose nevirapine to mothers and infants, have been effective in reducing transmission but at the cost of development of resistance. Strategies that will allow women to preserve their antiretroviral options when they will need therapy for their own HIV disease and will improve efficacy are urgently needed. Moreover, co-infection with hepatitis B virus (HBV) is a problem for a substantial proportion of HIV-infected pregnant women. HIV alters the course of HBV disease by increasing levels of HBV DNA replication and thus risk of transmission to the newborn. HBV immunization in the infant with the first dose started soon after birth has decreased the bulk of such transmission, but the risk remains, particularly for mothers with HBe antigen positivity. Ideally an antiviral regimen administered during pregnancy with activity against both viruses would minimize transmission of both HIV and HBV to the infant.

The investigators propose to study a combination of tenofovir/lamivudine/lopinavir-ritonavir started between 14 and 28 weeks of pregnancy in HIV and HBV co-infected women. This regimen provides potent antiviral activity for prevention of MTCT. In addition, tenofovir and lamivudine both have activity against HBV, and could play a role in decreasing transmission of HBV to the infant. This regimen will be compared to the WHO-recommended and locally practiced standard of care, consisting of zidovudine/lamivudine/lopinavir-ritonavir, also starting at 14-28 weeks of pregnancy. This will be a phase II study evaluating the safety of the test regimen in pregnant women and their newborns, in particular renal, bone mineral density and hepatic toxicity (including hepatic flares post discontinuation of therapy). The study will recruit 80 pregnant women of at least 20 years of age in China and follow them and their infants for 12 months post-delivery. The investigators will recruit from prenatal clinics in some of the districts most heavily affected by HIV in the Guangxi province in China. China is selected for this study as it is hyperendemic for hepatitis B and has a rising HIV epidemic. Although not powered to examine efficacy, preliminary estimates of transmission of HIV and HBV to the infants and of the rate of resistance development will be obtained. The study will be done in collaboration with CDC-GAP China and the Chinese Ministry of Health-National Center for AIDS, which will coordinate recruitment, study visits and data collection through the local HIV/AIDS coordinators.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Serologically-confirmed HIV and HBV infection
  • Gestational age less than 28 weeks
  • Willingness to participate in a clinical trial
  • Age 20 years or over on the day of inclusion
  • Willingness to return for follow-up visits and to allow infant participation in the trial
  • Intent to remain in the clinic catchment area during the duration of the study
  • No serious current complications of pregnancy
  • No previous or current use of antiretrovirals including the HIVNET 012 regiment
  • Hemoglobin over 8 g/dL
  • Blood creatinine clearance greater than or equal to 60 mL/min estimated by the Cockroft-Gault formula for women

Exclusion Criteria:

  • Age less than 20
  • Pregnant woman refuses to sign the consent to participate
  • Unwillingness to adhere to visit schedule or maintain adherence with medications
  • Illnesses so severe as to likely require maternal hospitalization
  • Intend to breastfeed
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01125696

Contacts
Contact: Sascha R Ellington, MSPH 770-488-6037 sellington@cdc.gov

Locations
China, Guangxi
Liuzhou MCH Hospital Recruiting
Liuzhou, Guangxi, China
Guangxi MCH Hospital Recruiting
Nanning, Guangxi, China
Contact: Liu Wei, MD    0771-2518308      
Contact: Lili Chen, Professor    0771-2826520      
Sponsors and Collaborators
National Center for AIDS/STD Control and Prevention, China CDC
Investigators
Principal Investigator: Athena P Kourtis, MD, PhD, MPH Centers for Disease Control and Prevention, Division of Reproductive Health
  More Information

No publications provided

Responsible Party: Athena Kourtis, Lead Medical Officer, Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01125696     History of Changes
Other Study ID Numbers: CDC-NCCDPHP-5877
Study First Received: March 29, 2010
Last Updated: February 3, 2014
Health Authority: United States: Federal Government

Keywords provided by Centers for Disease Control and Prevention:
mother-to-child transmission
HIV
Hepatitis B
Pregnant women
Tenofovir
Infants

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Zidovudine
Lamivudine
Tenofovir
Tenofovir disoproxil
Ritonavir
Lopinavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014