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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01125696
Recruitment Status : Completed
First Posted : May 18, 2010
Last Update Posted : July 15, 2020
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

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
HIV Hepatitis B Drug: Tenofovir/lamivudine/lopinavir-ritonavir Drug: Zidovudine/lamivudine/lopinavir-ritonavir Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : May 2012
Actual Primary Completion Date : May 2018
Actual Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
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


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

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

  3. Maternal Tenofovir Pharmacokinetics [ Time Frame: 16 weeks gestation through delivery ]
    Only for mothers on the active arm.

  4. Infant Tenofovir Pharmacokinetics [ Time Frame: one timepoint within 12 hours of delivery ]
    Only for infants on the active arm.

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


Secondary Outcome Measures :
  1. HBV viral load in mothers [ Time Frame: from baseline (14-28 weeks gestation) through delivery ]
  2. Infant HIV transmission rate [ Time Frame: birth through 12 months ]
  3. Infant HBV transmission rate [ Time Frame: birth through 12 months ]
  4. Prevalence of HIV resistance mutations [ Time Frame: from baseline (14-28 weeks gestation) through 12 months postpartum ]
  5. Prevalence of HBV resistance mutations [ Time Frame: from baseline (14-28 weeks gestation) through 12 months postpartum ]

Eligibility Criteria
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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes 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
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Information from the National Library of Medicine

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): NCT01125696


Locations
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China, Guangxi
Liuzhou MCH Hospital
Liuzhou, Guangxi, China
Guangxi MCH Hospital
Nanning, Guangxi, China
Sponsors and Collaborators
Centers for Disease Control and Prevention
National Center for AIDS/STD Control and Prevention, China CDC
Investigators
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Principal Investigator: Athena P Kourtis, MD, PhD, MPH Centers for Disease Control and Prevention, Division of Reproductive Health
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Athena Kourtis, Lead Medical Officer, Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01125696    
Other Study ID Numbers: CDC-NCCDPHP-5877
First Posted: May 18, 2010    Key Record Dates
Last Update Posted: July 15, 2020
Last Verified: July 2020
Keywords provided by Athena Kourtis, Centers for Disease Control and Prevention:
mother-to-child transmission
HIV
Hepatitis B
 Pregnant women
Tenofovir
Infants
Additional relevant MeSH terms:
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Hepatitis B
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Blood-Borne Infections
Communicable Diseases
Hepadnaviridae Infections
DNA Virus Infections
Ritonavir
Lopinavir
Tenofovir
Lamivudine
 Zidovudine
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Antimetabolites