Clinical trial NCT03869944: Preventing Childhood HIV: Rescue Intervention. ANRS 12388 PREVENIR-PEV
Official title: Elimination of Paediatric HIV-1 Infection: Evaluation of the Prevention Programme and Rescue Intervention Based on the Expanded Programme on Immunization (EPI). ANRS 12388 PREVENIR-PEV Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: HIV-1
Keywords: HIV-1
PMTCT
Point of Care
PrEP
Burkina Faso
Expanded Program of Immunization (EPI)
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: Centre Muraz
First posted: 2019-03-11
Enrollment: 97
Sex: FEMALE
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase II trial, non-randomized, open-label, mono-country and multi-center trial
Primary purpose: PREVENTION

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

Detailed description: The WHO recommendation of lifelong antiretroviral therapy (ART) for all HIV-infected pregnant or breastfeeding women represents a major advance for universal access to HIV care but this strategy alone may not be sufficient to eliminate pediatric HIV in the communities.

Presently, the impact of prevention of mother-to-child HIV transmission (PMTCT) programs in the communities is unclear. There is also no available rescue intervention able to identify postpartum women at high risk of transmission in order to offer them adequate HIV care and prevent HIV acquisition by their breastfed infants.

We hypothesize that the second visit for routine vaccination (Expanded Program of Immunization visit 2, EPI-2) represents a unique opportunity to link EPI and PMTCT programs and introduce rescue preventive and therapeutic interventions.

The study will assess the efficacy of the PMTCT cascade up to 2 months post-partum for all mothers attending the EPI-2 (Component 1). For Component 1, the target population will be all 32,100 women participating in EPI-2 and verbally consenting to participate to evaluate the PMTCT program up to 2 months postpartum.

The consent form for component 2 will be proposed to all HIV positive mothers of component 1 who meet the inclusion and non-inclusion criteria. HIV-1 viral load measurement of the mothers and the detection of HIV-1 DNA in their children will be assessed. Children infected with HIV-1 will be referred for immediate ART initiation.

For Component 2 - phase IIb trial (N = 300 mother-infant pairs) - the target population will be HIV positive breastfeeding mothers aged 15 years or older with a child whose tests so far do not reveal the existence of infection (at EPI-2 visit) to assess the effectiveness of a rescue intervention for Prevention of Mother-to-Child Transmission of HIV up to 12 months of age.

The target population to receive PrEP (lamivudine) until 12 months of age (or until confirmed end of breastfeeding) will be women with unsuppressed HIV-1 infection (≥1000 copies of HIV-1 RNA/ml) with a child whose tests to date (EPI-2 visit) do not reveal the existence of infection.

HIV-1 infected women with suppressed (\<1000 copies of HIV-1 RNA/ml) viral load at the time of the EPI-2 visit will be followed at 6 and 12 months. If at 6 months the mother become virally unsuppressed, her child will receive ARV medication up to 12 months of age (or the confirmed end of breastfeeding) to prevent infection.

The control group does not apply to this study. The overall mother-to-child transmission rate is the WHO target for the elimination of paediatric HIV-1: 5% at one year of life (consistent with a 3% postnatal transmission rate between 2 and 12 months of age of the child).

Eligibility criteria: For HIV+ women who give consent, the measurement of their HIV-1 viral load and the detection of HIV-1 DNA in their children will be assessed.

Inclusion Criteria:

A mother-child couple will be included in the Phase IIb trial if the child:

* is a singleton
* is breastfed at about 2 months and the mother intends to continue breastfeeding for at least 4 months (until her child is 6 months old)
* has a POC HIV-1 PCR negative test at about 2 months of age
* has a mother who:
* accompanies him to visit 2 of the EPI
* is over 20 years of age or over or is a minor from the age of 15 and is accompanied by a referent adult of his/her choice representing his/her interests (parent, family member or guardian, member of an association, etc.)
* has been confirmed to be infected with HIV-1 (with or without HIV-2)
* signature of the consent to participate
* for the mother signed by herself and a witness (if illiterate) and/or a referent adult (if under 20 years of age)
* for the child: consent must be signed by both parents unless the mother exercises parental authority alone or if obtaining the father's consent is likely to endanger the mother and her child.

Exclusion Criteria:

A mother-child couple will not be included in the Phase IIb trial if the child:

* exhibits DAIDS grade 3 or 4 clinical symptoms or biological anomalies for adverse events on the day of inclusion
* has a severe congenital malformation
* has a known allergy to the study drug or its components
* is taking emtricitabine concomitantly
* has a mother:
* living outside the study area or planning to move from the area within the next 12 months
* participating in another clinical trial on the day of inclusion

Primary outcomes:
measure: Prevention of HIV-1 transmission from HIV-1-positive mothers to their breastfeeding children
timeFrame: 12 months
Secondary outcomes:
measure: Efficacy of PMTCT cascade - mother
timeFrame: 2 months
measure: Efficacy of PMTCT cascade - child
timeFrame: 2 months
measure: Access to ART for HIV-1-positive children
timeFrame: 6 months
measure: Number of Adverse Events Grade 3 and 4 in the prevention of HIV-1 via breastfeeding [Safety of lamivudine]
timeFrame: 12 months
Other outcomes:
Locations:
city: Bobo-Dioulasso
country: Burkina Faso
facility: Paulin Fao
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Philippe Van de Perre, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.