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Infant Peri-Exposure Prophylaxis to Prevent HIV-1 Transmission by Breastfeeding: Mechanisms & Safety

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ClinicalTrials.gov Identifier: NCT03519503
Recruitment Status : Recruiting
First Posted : May 9, 2018
Last Update Posted : May 9, 2018
Sponsor:
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Brief Summary:

General objective

  • To assess the long-term safety and efficacy of one-year infant prophylaxis using lamivudine (3TC) or lopinavir/ritonavir (LPV/r) to prevent post-natal transmission through breastfeeding.
  • To investigate the biological mechanisms involved in postnatal HIV transmission.

Specific objectives

  • To compare the long-term safety of infant prophylaxis using either 3TC versus LPV/r on child development (growth, somatic and mental health), mortality, adrenal function, liver function, full blood count and mitochondrial toxicity.
  • To estimate the final efficacy data of 50 weeks of infant prophylaxis using either LPV/r or 3TC, since some mothers may have resumed breastfeeding after the trial.
  • To profile miRNA in breast milk according to maternal HIV status and HIV transmission.
  • To determine the influence of maternal milk on infant gut inflammation in an in vitro 3D-intestinal model (CACO-2 cells).

The study population will comprise all ANRS 12174 PROMISE-PEP trial participants who completed the 50 week follow-up and are not HIV infected. An estimate of 881 mother-child pairs from the ANRS 12174 PROMISE- PEP will be recruited.

This study is structured in two parts. The 'clinical & biological safety' component involves a cross sectional survey. A clinical and neuropsychological examination of participants will be conducted. In addition one venous blood sample will be collected to evaluate children HIV status, full blood count, liver & adrenal function and mitochondrial toxicity. Capillary hair follicles will be collected from 100 children in Zambia to study their genome integrity.

The 'mechanisms' component includes biological assays to be conducted on breast milk samples previously collected from HIV infected, transmitting or non-infected mothers enrolled at ANRS 12174 PROMISE-PEP trial.

Primary endpoint: Long term survival, mortality rate, measurements of infant growth (length and weight), somatic and neuropsychological development of the 5 year old children enrolled in the ANRS 12174 PROMISE- PEP trial.

Secondary endpoints: HIV seroconversion since last PROMISE PEP trial visit, full blood count, liver function, adrenal function, serum lactate. Number of mitochondrial DNA copies per cell & percentage of mitochondrial DNA deletion for mitochondrial toxicity. Number of micronuclei & number of Ɣ-tubulin spot per cell to study genomic toxicity.


Condition or disease
Growth and Development

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 880 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Promoting Infant Health and Nutrition in Sub-Saharan Africa (PROMISE): Safety and Efficacy of Infant Peri-Exposure Prophylaxis (PEP) to Prevent HIV-1 Transmission by Breastfeeding Mechanisms & Safety (M&S)
Actual Study Start Date : February 27, 2017
Estimated Primary Completion Date : April 30, 2018
Estimated Study Completion Date : April 30, 2018

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. HIV seroconversion [ Time Frame: From date of last visit in PROMISE PEP study (week 50 of follow-up) until the date of PROMISE-PEP M&S inclusion visit, assessed up to 96 months ]
    Number of children with positive HIV test


Secondary Outcome Measures :
  1. Long term survival [ Time Frame: From date of last visit in PROMISE PEP study (week 50 of follow-up) until the date of first documented date of death from any cause, assessed up to 96 months ]
    Time to death

  2. Mortality rate [ Time Frame: From date of last visit in PROMISE PEP study (week 50 of follow-up) until the date of first documented date of death from any cause, assessed up to 96 months ]
    Number of deaths

  3. Height [ Time Frame: Cross-sectional survey during the inclusion visit ]
    measured in centimeters

  4. Weight [ Time Frame: Cross-sectional survey during the inclusion visit ]
    measured in kilograms

  5. Infant growth [ Time Frame: Cross-sectional survey during the inclusion visit ]
    weight-for-height, height for age, weight for age and body mass index for age measured by Z-scores

  6. Neuro-psychological development [ Time Frame: Cross-sectional survey during the inclusion visit ]
    Development measured by M-ABC2, KABC-II, SDQ25 and TOVA-visual total standard test scores, percentiles, age specific norms and standard deviations.

  7. Biological disorders [ Time Frame: Cross-sectional survey during the inclusion visit ]
    Number of children with normal full blood count

  8. Biological disorders [ Time Frame: Cross-sectional survey during the inclusion visit ]
    Number of children with normal liver function tests

  9. Biological disorders [ Time Frame: Cross-sectional survey during the inclusion visit ]
    Number of children with normal functioning of adrenal glands

  10. Biological disorders [ Time Frame: Cross-sectional survey during the inclusion visit ]
    Number of children with normal serum lactate levels


Other Outcome Measures:
  1. Mitochondrial toxicity [ Time Frame: Cross-sectional survey during the inclusion visit ]
    Number of mitochondrial DNA copies per cell

  2. Mitochondrial toxicity [ Time Frame: Cross-sectional survey during the inclusion visit ]
    Percentage of mitochondrial DNA deletion

  3. Genome integrity [ Time Frame: Cross-sectional survey during the inclusion visit ]
    Number of micronuclei

  4. Genome integrity [ Time Frame: Cross-sectional survey during the inclusion visit ]
    Number of Ɣ-tubulin spot per cell


Biospecimen Retention:   Samples Without DNA
plasma


Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 8 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The study population will comprise all ANRS 12174 PROMISE-PEP trial participants who completed the 50 week follow-up and are not HIV infected. There are 1101 children fulfilling the inclusion criteria over the four African sites with an estimation of 80% of them being recruited on PROMISE M&S study (N=881).
Criteria

Inclusion Criteria:

  • Having taken part in the ANRS 12174 PROMISE-PEP trial until the final (50 week) visit;
  • Not being infected with HIV during the duration of the ANRS 12174 PROMISE-PEP trial.

Exclusion Criteria:

  • Parent refusal to participate in the study after information about the PROMISE M&S project is given.

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): NCT03519503


Contacts
Contact: Philippe VANDE PERRE, MD, PhD (+33) 34 35 91 11 p-van_de_perre@chu-montpellier.fr
Contact: Nicolas NAGOT, MD, PhD (+33) 34 35 91 09 n-nagot@chu-montpellier.fr

Locations
Burkina Faso
Centre Hospitalier Universitaire Blaise Compraore Recruiting
Ouagadougou, Burkina Faso
Contact: Souleymane TASSEMBEDO, MD         
South Africa
Cecilia Makiwane hospital Recruiting
East London, South Africa
Contact: Mandisa SINGATA, PhD         
Uganda
PROMISE M&S site Recruiting
Mbale, Uganda
Contact: Grace N'DEEZI, MD,PhD         
Zambia
Paediatric Center Of Excellence Recruiting
Lusaka, Zambia
Contact: Mwiya MWIYA, MD         
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
Principal Investigator: Chipepo KANKASA, MD, PhD University of Zambia
Principal Investigator: Mandisa SINGATA, PhD University of Fort Hare, South Africa
Principal Investigator: Nicolas MEDA, MD, PhD University of Ouagadougou, Burkina Faso
Principal Investigator: James K TUMWINE, MD,PhD University of Makerere, Uganda

Publications:
Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT03519503     History of Changes
Other Study ID Numbers: ANRS 12341 PROMISE-PEP M&S
First Posted: May 9, 2018    Key Record Dates
Last Update Posted: May 9, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HIV
Neuropsychological tests
PMTCT
PreP