Prevention of Mother-to-child Transmission of HIV-1 Using a Responsive Intervention

NCT03870438 | Completed Phase 3 DMC

• 1 other identifier: ANRS 12397 PROMISE-EPI
• Study Type: interventional
• Target: 1,506
• Locations: 2 countries
• Sites: 6

Brief Summary

The second visit of the Expanded Programme of Immunization when the child is 2 months old (EPI-2) represents a unique opportunity to link the EPI and PMTCT programmes and to introduce preventive and therapeutic rescue interventions in order to: 1) Assess the efficacy of the PMTCT cascade up to 2 months postpartum; 2) Allow at least 80% of HIV-1-infected infants identified at the second EPI visit who were not involved in HIV care to initiate ARVs at the earliest, but no later than 2 months after confirmation of HIV diagnosis; 3) Reduce HIV-1 transmission to less than 3% between 2 and 12 months among exposed children who completed the second EPI visit

Conditions

HIV-1

Keywords

HIV-1; PMTCT; Point of Care; PrEP; Zambia; Burkina Faso; Expanded Program of Immunization (EPI)

Outcome Measures

Primary Outcomes (1)

• Prevention of HIV-1 transmission from HIV-1-positive mothers to their breastfeeding children

  Postnatal HIV-1 transmission rates at 12 months in infants exposed to HIV-1 through breastfeeding

  12 months

Secondary Outcomes (9)

• Assessment of PMTCT cascade

  2 months

• Access to ART for HIV-1 positive children

  6 months

• Evaluation of the diagnostic performance of plasma HIV viral load in comparison to breastmilk viral load to identify infants at risk of transmission at 6-8 weeks, 6 months and 12 months

  6-8 weeks, 6 months, 12 months

• Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population following the 2020 Zambian guidelines implementation:

  12 months

• Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population following the 2020 Zambian guidelines implementation:

  12 months

Study Arms (2)

Intervention

EXPERIMENTAL

Children infected with HIV-1 will be referred to the National Programme for confirmed HIV diagnosis and immediate ART. For children that are not HIV-1 infected, the results on the mother's viral load will guide the next steps: Mothers with a detectable plasma viral load (≥ 1000 copies/mL): their children will be initiated on lamivudine oral solution. Mothers with an undetectable viral loads (\<1000 copies/mL): their children will not be initiated on lamivudine oral solution at 6-8 weeks of age. However, additional monitoring on the viral load of the mother and the diagnosis of the child will take place at 6 months: If the maternal plasmatic viral load is ≥ 1000 copies/mL, the child will be initiated on lamivudine oral solution.

Drug: Lamivudine Oral Solution

Control

NO INTERVENTION

Routine Option B+ national guidelines including HIV-1 plasmatic viral load testing will be adhered to. Visits will take place at 6-8 weeks, 6 and 12 months post-partum to collect samples from the mother for the analysis of viral load results at 12 months. In addition, at 6-8 weeks, 6 and 12 months post-partum, POC tests will be done for the diagnosis of HIV-1 in their infants (by HIV-1 DNA PCR) and results will be shared within 2 hours. Children infected with HIV-1 will be referred to the National Programme for confirmed diagnosis and immediate ART.

Interventions

Lamivudine Oral Solution DRUG

In the intervention arm, HIV-1 negative children with HIV-1 positive mothers who have an HIV-1 viral load ≥ 1000 copies/ml will receive lamivudine syrup orally (7.5 mg twice daily if 2 to 4 kg; 25 mg twice a day if weight \<8 kg; and 50 mg twice a day if weight \>8 kg). The intervention will last a maximum of 10 months (until the baby is 12 months old or until the confirmed end of breastfeeding). Breastfeeding will be considered to be ceased if the mother confirms she is no longer breastfeeding for 2 consecutive monthly visits

Intervention

Eligibility Criteria

• Age: 15 Years+
• Gender Eligibility Details: HIV-1-positive breastfeeding mothers of HIV-1-negative children (female or male)
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• A mother/infant pair will be included in the Phase III trial if the infant:
• Is a singleton
• Is breastfed at 2 months and the mother intends to continue breastfeeding for at least 4 months (until her child is 6 months old)
• Has a negative HIV-1 PCR POC test at 2 months of age
• Has a mother who:
• Is the accompanying person to visit 2 of the EPI
• Is 15 years of age or older (in Zambia) and 20 years of age or older (in Burkina Faso) or
• If between 15 and 19 years of age (inclusive) in Burkina Faso, and is accompanied by a referent adult of her choice representing her interests and the interests of the child (parent, family member or guardian, member of an association, etc.)
• Has been confirmed to be infected with HIV-1 (with or without HIV-2)
• Has signed the consent form to participate For the mother in Zambia, the consent must be signed by herself and a witness; For the mother in Burkina Faso, the consent must be signed by herself and a witness (if illiterate) and/or a referent adult (if under 20 years of age in Burkina Faso).
• For the child in Zambia, the consent must be signed by the mother. For the child in Burkina Faso, the consent must be signed by the mother and/or a referent adult (if under 20 years of age in Burkina Faso. In Burkina Faso, both parents need to sign the consent unless the mother exercises sole parental authority or if obtaining the father's consent is likely to endanger the mother and her child. In Zambia, the mother exercises sole parental authority.

You may not qualify if:

• A mother-child couple will not be included if the child:
• Has a severe congenital malformation
• Has a known allergy to the study drug or its components
• Takes emtricitabine concomitantly
• Has a mother who:
• Lives outside the study area or intending to move from the area within the next 12 months
• Is participating in another clinical trial

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• University Teaching Hospital, Lusaka, Zambia: collaborator
• Centre Muraz: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• University of Bergen: collaborator

Study Sites (6)

CSPS and CMA of Do and Dafra districts

Bobo-Dioulasso, Burkina Faso

Location

CSPS and CMA of Baskuy and Boulmiougou districts

Ouagadougou, Burkina Faso

Location

Bauleni

Lusaka, Zambia

Location

Chaisa

Lusaka, Zambia

Location

Chilenje Level 1 hospital

Lusaka, Zambia

Location

Matero Main

Lusaka, Zambia

Location

Related Publications (3)

• 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

• Mennecier A, Kankasa C, Fao P, Moles JP, Eymard-Duvernay S, Mwiya M, Kania D, Chunda-Liyoka C, Sakana L, Rutagwera D, Tassembedo S, Wilfred-Tonga MM, Mosqueira B, Tylleskar T, Nagot N, Van de Perre P; ANRS 12397 Study group. Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso. Contemp Clin Trials. 2021 Jun;105:106402. doi: 10.1016/j.cct.2021.106402. Epub 2021 Apr 17.

  PMID: 33872801 BACKGROUND

• Kankasa C, Mennecier A, Sakana BLD, Moles JP, Mwiya M, Chunda-Liyoka C, D'Ottavi M, Tassembedo S, Wilfred-Tonga MM, Fao P, Rutagwera D, Matoka B, Kania D, Taofiki OA, Tylleskar T, Van de Perre P, Nagot N; PROMISE-EPI Trial Group. Optimised prevention of postnatal HIV transmission in Zambia and Burkina Faso (PROMISE-EPI): a phase 3, open-label, randomised controlled trial. Lancet. 2024 Apr 6;403(10434):1362-1371. doi: 10.1016/S0140-6736(23)02464-9. Epub 2024 Mar 11.

  PMID: 38484756 DERIVED

MeSH Terms

Interventions

Lamivudine

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Philippe Van de Perre, MD, PhD

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Phase III, Randomized Control Trial, parallel, open-label, multi-country and multi-centre trial

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 12, 2019
• Study Start: December 14, 2019
• Primary Completion: September 12, 2022
• Study Completion: October 31, 2022
• Last Updated: December 7, 2022

Record last verified: 2022-12

Locations

BU (2); ZA (4)