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Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial (LEOPARD)

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Louise Kuhn, Columbia University
Sponsor:
Collaborators:
National Institutes of Health (NIH)
University of Witwatersrand, South Africa
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Louise Kuhn, Columbia University
ClinicalTrials.gov Identifier:
NCT02431975
First received: April 28, 2015
Last updated: July 18, 2017
Last verified: July 2017
  Purpose

The investigators propose a non-randomized clinical trial of 60 HIV-infected infants identified within 48 hours of birth and their mothers to investigate the consequences of very early ART on the establishment and maintenance of the viral reservoir.

The first phase (early ART initiation within 48 hours of birth) will examine the trajectory i.e. changes over time of the viral reservoir and detection of HIV-specific antibody responses in infants testing HIV-positive within 48 hours of birth and initiating early ART.

Secondary pathogenesis aims will test whether markers of neonatal immune quiescence are associated with the extent of seeding and rate of decline of the viral reservoir when ART is started at a young age and investigate whether markers in infant stool samples can be used as a non-invasive method of defining relevant immune and HIV-specific parameters associated with viral reservoir size.

The investigators hypothesize that developmental characteristics of newborn immunity may make this period the optimal time to begin ART and influence the seeding of the viral reservoir.


Condition Intervention Phase
HIV Drug: Nevirapine Drug: Zidovudine Drug: Lamivudine Drug: LPV/r Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial

Resource links provided by NLM:


Further study details as provided by Louise Kuhn, Columbia University:

Primary Outcome Measures:
  • Percent of patients with initial viral suppression [ Time Frame: 24 weeks ]
    Suppression is defined as patients with plasma HIV RNA <50 copies/mL.


Secondary Outcome Measures:
  • Percent of patients maintaining viral suppression [ Time Frame: Between 24 and104 weeks ]
    Suppression is defined as patients with plasma HIV RNA <50 copies/mL.

  • Prevalence of CD4 percentage greater than 30 [ Time Frame: By 24 weeks and sustained through 104 weeks ]
    Patients that reached a normal CD4% level.

  • Prevalence of growth along curve within one standard deviation or upward trend [ Time Frame: Up to 104 weeks ]
    By comparing viral growth curves.

  • Prevalence of detection of specific HIV antibody classes [ Time Frame: 24 and 104 weeks ]
    HIV antibody detection

  • Size of the viral reservoir (copies/million cell) [ Time Frame: Up to 104 weeks ]
    Quantification of viral reservoir


Estimated Enrollment: 60
Actual Study Start Date: August 2015
Estimated Study Completion Date: July 31, 2020
Estimated Primary Completion Date: July 31, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Early ART
All infants enrolled in the trial, regardless of maternal PMTCT regimen, will be initiated on a triple ARV regimen consisting of nevirapine (NVP), zidovudine (ZDV) and lamivudine (3TC) presumptively based on the initial positive result. This regimen will be continued to 42 weeks post menstrual age (PMA). At this time, infants will be switched to LPV/r, ZDV and 3TC to be continued to 104 weeks or longer unless otherwise preferred by the treating clinician or if any clinical or laboratory contraindications are identified.
Drug: Nevirapine

Standard medication used to treat and prevent HIV/AIDS, specifically HIV-1. It is generally recommended for use with other antiretroviral medication.

The initial dose of NVP will be 6 mg per kg per dose orally twice daily until 42 weeks gestational age (2 weeks of age for infants born at term) which is the dosing selected by the NIH International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Network.

Other Names:
  • NVP
  • Viramune
Drug: Zidovudine

An antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretroviral.

ZDV will be dosed as per standard guideline and routine practices.

Other Names:
  • ZDV
  • Retrovir
Drug: Lamivudine

An antiretroviral medication used to prevent and treat HIV/AIDS. It is effective against both HIV-1 and HIV-2.

3TC will be dosed as per standard guideline and routine practices.

Other Names:
  • 3TC
  • Epivir
Drug: LPV/r

Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir.

LPV/r will be dosed as per standard guideline and routine practices.

Other Name: Ritonavir-boosted lopinavir

Detailed Description:
Prevention of mother-to-child transmission (PMTCT) programs using antiretrovirals (ARVs) have had tremendous success in sub-Saharan Africa. However, HIV transmission continues to occur because (1) implementation of PMTCT is incomplete and (2) ARV interventions are not 100% effective in blocking infection. Thus the challenge of providing treatment to HIV-infected children is far from over. The capacity of early ART treatment to favorably influence the viral reservoir and potentially lead to post-treatment cessation viral control needs to be described in the population of infants, and to identify useful public health strategies.
  Eligibility

Ages Eligible for Study:   up to 48 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Point of care (POC) or laboratory-based test positive on a sample collected within 48 hours of birth.
  • Mother willing and able to provide informed consent.

Exclusion Criteria:

  • Expressed intention to leave the Johannesburg area permanently.
  • Co-morbidities, birth defects or other conditions which in the opinion of the clinical team have a greater than 50% risk of mortality in the first days of life.
  • Co-morbidities or conditions which in the opinion of the clinical team advise against initiation of ART within the first 48 hours of life.
  • Active (uncontrolled) maternal psychiatric illness.
  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: NCT02431975

Contacts
Contact: Louise Kuhn, PhD lk24@columbia.edu

Locations
South Africa
Rahima Moosa Mother and Child Hospital Recruiting
Johannesburg, Gauteng, South Africa
Contact: Ashraf Coovadia, MBChB    +27 114709290    Ashraf.Coovadia@wits.ac.za   
Contact: Karl Technau, MBChB       karltechnau@gmail.com   
Sponsors and Collaborators
Columbia University
National Institutes of Health (NIH)
University of Witwatersrand, South Africa
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Louise Kuhn, PhD Columbia University
  More Information

Responsible Party: Louise Kuhn, Professor of Epidemiology, Department of Epidemiology, Columbia University
ClinicalTrials.gov Identifier: NCT02431975     History of Changes
Other Study ID Numbers: AAAO5011
U01HD080441 ( U.S. NIH Grant/Contract )
Study First Received: April 28, 2015
Last Updated: July 18, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Louise Kuhn, Columbia University:
HIV
infant
antiretroviral therapy, highly active
antiretroviral agents

Additional relevant MeSH terms:
Ritonavir
Lopinavir
Lamivudine
Zidovudine
Nevirapine
HIV 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
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers

ClinicalTrials.gov processed this record on September 25, 2017