NCT03519503

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

Completed Last updated 8 August 2019

What this trial tests

trial in Growth and Development in 562 participants. Completed in 15 February 2018.

Timeline

27 February 2017

Primary endpoint
13 February 2018

15 February 2018

Quick facts

Lead sponsor	ANRS, Emerging Infectious Diseases
Status	Completed
Study type	OBSERVATIONAL
Enrollment	562
Start date	27 February 2017
Primary completion	13 February 2018
Estimated completion	15 February 2018
Sites	4 locations across Zambia, South Africa, Uganda, Burkina Faso

Conditions studied

• Growth and Development — all drugs for Growth and Development →

Sponsor

ANRS, Emerging Infectious Diseases — full company profile →

Who can join

Adults 5 to 8, any sex, with Growth and Development. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Health Outcomes at School Age among Children Who Are HIV-Exposed but Uninfected with Detected Mitochondrial DNA Depletion at One Year.
   Monnin A, Nagot N, Eymard-Duvernay S, Meda N, et al · · 2020 · cited 6× · PMID 33207772 · DOI 10.3390/jcm9113680
2. Long-Term Persistence of Mitochondrial DNA Instability in HIV-Exposed Uninfected Children during and after Exposure to Antiretroviral Drugs and HIV.
   Desquiret-Dumas V, D'Ottavi M, Monnin A, Goudenège D, et al · · 2022 · cited 5× · PMID 35892686 · DOI 10.3390/biomedicines10081786
3. Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis.
   Monnin A, Vizeneux A, Nagot N, Eymard-Duvernay S, et al · · 2021 · cited 3× · PMID 34572228 · DOI 10.3390/children8090796