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

NCT03519503 | Completed

• 1 other identifier: ANRS 12341 PROMISE-PEP M&S
• Study Type: observational
• Target: 562
• Locations: 3 countries
• Sites: 3

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.

Conditions

Growth and Development

Keywords

HIV; Neuropsychological tests; PMTCT; PreP

Outcome Measures

Primary Outcomes (1)

• HIV seroconversion

  Number of children with positive HIV test

  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

Secondary Outcomes (10)

• Long term survival

  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

• Mortality rate

  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

• Height

  Cross-sectional survey during the inclusion visit

• Weight

  Cross-sectional survey during the inclusion visit

• Infant growth

  Cross-sectional survey during the inclusion visit

Other Outcomes (4)

• Mitochondrial toxicity

  Cross-sectional survey during the inclusion visit

• Mitochondrial toxicity

  Cross-sectional survey during the inclusion visit

• Genome integrity

  Cross-sectional survey during the inclusion visit

Eligibility Criteria

• Age: 5 Years - 8 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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).

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (4)

Centre Hospitalier Universitaire Blaise Compraore

Ouagadougou, Burkina Faso

Location

Cecilia Makiwane hospital

East London, South Africa

Location

PROMISE M&S site

Mbale, Uganda

Location

Paediatric Center Of Excellence

Lusaka, Zambia

Location

Related Publications (3)

• Heidari S, Mofenson L, Cotton MF, Marlink R, Cahn P, Katabira E. Antiretroviral drugs for preventing mother-to-child transmission of HIV: a review of potential effects on HIV-exposed but uninfected children. J Acquir Immune Defic Syndr. 2011 Aug 1;57(4):290-6. doi: 10.1097/QAI.0b013e318221c56a.

  PMID: 21602695 BACKGROUND

• Van de Perre P, Rubbo PA, Viljoen J, Nagot N, Tylleskar T, Lepage P, Vendrell JP, Tuaillon E. HIV-1 reservoirs in breast milk and challenges to elimination of breast-feeding transmission of HIV-1. Sci Transl Med. 2012 Jul 18;4(143):143sr3. doi: 10.1126/scitranslmed.3003327.

  PMID: 22814853 BACKGROUND

• Nagot N, Kankasa C, Tumwine JK, Meda N, Hofmeyr GJ, Vallo R, Mwiya M, Kwagala M, Traore H, Sunday A, Singata M, Siuluta C, Some E, Rutagwera D, Neboua D, Ndeezi G, Jackson D, Marechal V, Neveu D, Engebretsen IMS, Lombard C, Blanche S, Sommerfelt H, Rekacewicz C, Tylleskar T, Van de Perre P; ANRS 12174 Trial Group. Extended pre-exposure prophylaxis with lopinavir-ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial. Lancet. 2016 Feb 6;387(10018):566-573. doi: 10.1016/S0140-6736(15)00984-8. Epub 2015 Nov 19.

  PMID: 26603917 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: May 9, 2018
• Study Start: February 27, 2017
• Primary Completion: February 13, 2018
• Study Completion: February 15, 2018
• Last Updated: August 8, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1); UG (1); ZA (1)