HIV-1Phase 3PROMISE-EPINCT03870438
Prevention of Mother-to-child Transmission of HIV-1 Using a Responsive Intervention
A Phase 3 study testing Lamivudine Oral Solution in people with HIV-1, run by ANRS, Emerging Infectious Diseases at 6 sites in 2 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 15 years and older, women only
- Conditions the study is for
- HIV-1
- What is being tested?
- Lamivudine Oral Solution
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,506 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 14 Dec 2019to 31 Oct 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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.
Who cannot join
- A mother-child couple will not be included if the child:
- Has clinical symptoms or biological abnormalities of DAIDS classification 3 or 4 for adverse events on the day of inclusion
- 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
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Zambia4 sites
Bauleni
Lusaka
Chaisa
Lusaka
Chilenje Level 1 hospital
Lusaka
Matero Main
Lusaka
Burkina Faso2 sites
CSPS and CMA of Do and Dafra districts
Bobo-Dioulasso
CSPS and CMA of Baskuy and Boulmiougou districts
Ouagadougou
About this study
Official title: Prevention of Mother-to-child Transmission of HIV-1: Programme Evaluation and Innovative Responsive Intervention Integrated in the Expanded Programme of Immunization. PROMISE-EPI Study
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
Read the detailed description
In the vast majority of sub-Saharan African countries, all mothers attend an immunization (EPI) visit when their child is 6 to 8 weeks old (the first EPI visit for BCG and OPV0 vaccination, takes place at childbirth).
This study primarily aims at utilizing existing strategies to prevent postnatal HIV-1 transmission through optimizing the use of lamivudine as pre-exposure prophylaxis (PrEP) for at risk children. For this purpose, the study will use recently marketed diagnostic point of care (POC) tests at the first level of care for maternal HIV-1 viral load and early infant diagnosis (EID). This POC early infant diagnosis will also allow optimizing treatment of HIV-infected infants by offering to all the benefits of an early ART initiation.
The hypothesis is 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 EPI visit will allow an opportunity to:
- Assess the efficacy of the PMTCT cascade.
- Identify HIV-1-infected children early and refer them for early initiation of treatment
- Provide their children with an antiretroviral drug that can protect them from HIV-1, irrespective of their mother's adherence to ART as part of the Phase III Randomized Controlled Trial.
The Phase III RCT will be testing a rescue preventive intervention among HIV-1-uninfected children exposed to HIV-1 by their HIV-1-infected breastfeeding mothers against a control routine Option B+ implementation.
Following a brief questionnaire and counselling on ART adherence and breastfeeding, participant mothers aged 15 years or older who meet eligibility criteria will be randomized to the control or intervention arms at a 1:1 ratio.
The phase III Randomised Controlled Trial (RCT) testing a rescue preventive intervention among HIV-1-uninfected children exposed to HIV-1 by their HIV-1-infected breastfeeding mothers against a control routine Option B+ implementation.
In the control arm, routine Option B+ national guidelines including HIV-1 plasmatic viral load testing will be adhered to as part of the clinics' usual practice. 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.
The intervention arm aims at reducing the risk of HIV transmission for infants exposed to large amounts of HIV-1 through breastfeeding, which correlates with the maternal plasma viral load. At 6-8 weeks post-partum, a venous blood sample will be taken from the mothers to assess their viral load using a GenXpert® HIV RNA POC test. Concomitantly, a capillary blood sample will be taken from the child for the detection of HIV-1 (by HIV-1 DNA PCR). 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 in the intervention arm, the results on the mother's viral load will guide the next steps:
- Mothers with a detectable plasma viral load (≥ 1000 copies/mL) will receive reinforced counselling on ART adherence.
In addition, their child will be initiated on PrEP, lamivudine syrup (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). Mothers will come with their child to the study site every month (at M3, M4, M5, M7, M8, M9, M10 and M11) to collect drug supplies, safety follow-up, child's PrEP adherence adherence and counselling, mother's ART adherence and reporting. In Zambia, high risk HIV negative infants on a 12-week prophylactic regimen and are still taking ART at this visit, their first day of the study prophylaxis administration will take place at Month 3.
- Mothers with an undetectable viral loads (<1000 copies/mL) will continue receiving ART adherence counselling. However, the children of these mothers will not be initiated on PrEP on the study at 6-8 weeks of age. However, because ART compliance declines rapidly over time within the first year of initiation, 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 PrEP, lamivudine syrup (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), 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.
Children infected with HIV-1 will be referred to the National Programme for confirmed diagnosis and immediate ART.
- Conditions
- HIV-1
- Being tested
- Lamivudine Oral Solution
- Keywords
- HIV-1, PMTCT, Point of Care, PrEP, Zambia, Burkina Faso, Expanded Program of Immunization (EPI)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lamivudine Oral SolutionDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (9)
Assessment of PMTCT cascade
Proportion of women attending the 6-8 week EPI visit who, per the records in the antenatal care clinics:
- had attended ANC/PMTCT clinic at least once during their pregnancy
- had been tested for HIV-1 antenatally or during childbirth
- are HIV-1 infected Proportion of children who were HIV-1 tested with PCR at birth (Zambia only) (per the records in the antenatal care or birth clinics)
Proportion of women with a positive HIV test who had:
- initiated ART during pregnancy or following childbirth (per the records in the antenatal care clinics)
- undetectable plasma viral load (<1000 HIV RNA copies/mL) as per the results obtained with the Point of Care HIV-1 PCR Viral Load in the study Proportion of babies with a positive HIV-1 PCR (as per the results obtained with the Point of Care HIV-1 PCR Qualitative in the study)
Measured: 2 months
Access to ART for HIV-1 positive children
Proportion of HIV-infected infants identified during the second EPI visit and who were not engaged in HIV care at this time, but who will be initiated on ART within 2 months after this visit, or if infected during follow-up- within 2 months after diagnosis, (as per the results obtained with the Point of Care HIV-1 PCR Qualitative in the study)
Measured: 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
Proportion of plasma HIV-1 viral load levels concordant with breast milk HIV-1 viral load levels
Measured: 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:
To assess the non-inferiority of a single-drug versus triple-drug prophylactic regimen to prevent HIV transmission at one year of age (HIV-transmission rate from EPI-2 visit to 12 months of age)
Measured: 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:
To assess the non-inferiority of a single-drug versus triple-drug prophylactic regimen in terms of HIV-1 free survival at one year of age.
Measured: 12 months
Evaluation of the safety for all the participants of the intervention arm and the comparison arm sub-population following the 2020 Zambian guidelines implementation
Adverse events rates at 12 months, including death and Grade 3 or 4 events on the paediatric DAIDS scale
Measured: 12 months
Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population before the introduction of the 2020 Zambian guidelines (including Burkina Faso control arm)
To assess the efficacy of a responsive intervention package to prevent HIV transmission at one year of age (HIV-transmission rate from EPI-2 visit to 12 months of age)
Measured: 12 months
Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population before the introduction of the 2020 Zambian guidelines (including Burkina Faso control arm)
To assess the efficacy of a responsive intervention package to improve HIV-1 free survival at one year of age
Measured: 12 months
Evaluation of the safety for all the participants of the intervention arm and the comparison arm sub-population before the introduction of the 2020 Zambian guidelines (including Burkina Faso control arm)
Adverse events rates at 12 months, including death and Grade 3 or 4 events on the paediatric DAIDS scale
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2019
- Study start14 Dec 2019
- Primary completion12 Sep 2022
- Study completion31 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV-1Studies of the same condition, open and under way.
- More trials run by ANRS, Emerging Infectious DiseasesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase III, Randomized Control Trial, parallel, open-label, multi-country and multi-centre trial
- Masking
- None (open label)
- Enrolment
- 1,506 participants (actual)
Sponsor and investigators
- Lead sponsor
- ANRS, Emerging Infectious Diseases
- Sponsor type
- Other government
- Collaborators
- University Teaching Hospital, Lusaka, Zambia, Centre Muraz, Institut National de la Santé Et de la Recherche Médicale, France, University of Bergen
- Responsible party
- Sponsor
- Investigators
- Philippe Van de Perre, MD, PhD, Principal investigator, Institut National de la Santé Et de la Recherche Médicale, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03870438
- Sponsor's protocol ID
- ANRS 12397 PROMISE-EPI
- Acronym
- PROMISE-EPI
- Status last verified
- Dec 2022
- First submitted
- 4 Mar 2019
- Last updated
- 7 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 26603917Mennecier 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.
PubMed 33872801Kankasa 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.
PubMed 38484756
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Mother-to-child Transmission of HIV-1: Programme Evaluation and Innovative Responsive Intervention Integrated in the Expanded Programme of Immunization. PROMISE-EPI Study
- ClinicalTrials.gov ID
- NCT03870438
- Acronym / sponsor ID
- PROMISE-EPI / ANRS 12397 PROMISE-EPI
- Conditions
- HIV-1
- Keywords
- HIV-1, PMTCT, Point of Care, PrEP, Zambia, Burkina Faso, Expanded Program of Immunization (EPI)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,506 participants (actual)
- Lead sponsor
- ANRS, Emerging Infectious DiseasesOther government
- Collaborators
- University Teaching Hospital, Lusaka, Zambia, Centre Muraz, Institut National de la Santé Et de la Recherche Médicale, France, University of Bergen
- Study start
- 14 Dec 2019 (actual)
- Primary completion
- 12 Sep 2022 (actual)
- Study completion
- 31 Oct 2022 (actual)
- First posted
- 12 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
In the vast majority of sub-Saharan African countries, all mothers attend an immunization (EPI) visit when their child is 6 to 8 weeks old (the first EPI visit for BCG and OPV0 vaccination, takes place at childbirth).
This study primarily aims at utilizing existing strategies to prevent postnatal HIV-1 transmission through optimizing the use of lamivudine as pre-exposure prophylaxis (PrEP) for at risk children. For this purpose, the study will use recently marketed diagnostic point of care (POC) tests at the first level of care for maternal HIV-1 viral load and early infant diagnosis (EID). This POC early infant diagnosis will also allow optimizing treatment of HIV-infected infants by offering to all the benefits of an early ART initiation.
The hypothesis is 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 EPI visit will allow an opportunity to:
- Assess the efficacy of the PMTCT cascade.
- Identify HIV-1-infected children early and refer them for early initiation of treatment
- Provide their children with an antiretroviral drug that can protect them from HIV-1, irrespective of their mother's adherence to ART as part of the Phase III Randomized Controlled Trial.
The Phase III RCT will be testing a rescue preventive intervention among HIV-1-uninfected children exposed to HIV-1 by their HIV-1-infected breastfeeding mothers against a control routine Option B+ implementation.
Following a brief questionnaire and counselling on ART adherence and breastfeeding, participant mothers aged 15 years or older who meet eligibility criteria will be randomized to the control or intervention arms at a 1:1 ratio.
The phase III Randomised Controlled Trial (RCT) testing a rescue preventive intervention among HIV-1-uninfected children exposed to HIV-1 by their HIV-1-infected breastfeeding mothers against a control routine Option B+ implementation.
In the control arm, routine Option B+ national guidelines including HIV-1 plasmatic viral load testing will be adhered to as part of the clinics' usual practice. 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.
The intervention arm aims at reducing the risk of HIV transmission for infants exposed to large amounts of HIV-1 through breastfeeding, which correlates with the maternal plasma viral load. At 6-8 weeks post-partum, a venous blood sample will be taken from the mothers to assess their viral load using a GenXpert® HIV RNA POC test. Concomitantly, a capillary blood sample will be taken from the child for the detection of HIV-1 (by HIV-1 DNA PCR). 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 in the intervention arm, the results on the mother's viral load will guide the next steps:
- Mothers with a detectable plasma viral load (≥ 1000 copies/mL) will receive reinforced counselling on ART adherence.
In addition, their child will be initiated on PrEP, lamivudine syrup (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). Mothers will come with their child to the study site every month (at M3, M4, M5, M7, M8, M9, M10 and M11) to collect drug supplies, safety follow-up, child's PrEP adherence adherence and counselling, mother's ART adherence and reporting. In Zambia, high risk HIV negative infants on a 12-week prophylactic regimen and are still taking ART at this visit, their first day of the study prophylaxis administration will take place at Month 3.
- Mothers with an undetectable viral loads (<1000 copies/mL) will continue receiving ART adherence counselling. However, the children of these mothers will not be initiated on PrEP on the study at 6-8 weeks of age. However, because ART compliance declines rapidly over time within the first year of initiation, 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 PrEP, lamivudine syrup (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), 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.
Children infected with HIV-1 will be referred to the National Programme for confirmed diagnosis and immediate ART.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase III, Randomized Control Trial, parallel, open-label, multi-country and multi-centre trial
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Lamivudine Oral SolutionChildren 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. |
| 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. |
Who may qualify
- Ages
- 15 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (8 listed)
- Has clinical symptoms or biological abnormalities of DAIDS classification 3 or 4 for adverse events on the day of inclusion
- Has a severe congenital malformation
- Has a known allergy to the study drug or its components
- Takes emtricitabine concomitantly
- Has a mother who:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lamivudine Oral SolutionIn 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 | Drug | Intervention |
Primary outcome
Prevention of HIV-1 transmission from HIV-1-positive mothers to their breastfeeding children
Time frame: 12 months
Postnatal HIV-1 transmission rates at 12 months in infants exposed to HIV-1 through breastfeeding
9 secondary outcomes
Assessment of PMTCT cascade
Time frame: 2 months
Access to ART for HIV-1 positive children
Time frame: 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
Time frame: 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:
Time frame: 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:
Time frame: 12 months
Evaluation of the safety for all the participants of the intervention arm and the comparison arm sub-population following the 2020 Zambian guidelines implementation
Time frame: 12 months
Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population before the introduction of the 2020 Zambian guidelines (including Burkina Faso control arm)
Time frame: 12 months
Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population before the introduction of the 2020 Zambian guidelines (including Burkina Faso control arm)
Time frame: 12 months
Evaluation of the safety for all the participants of the intervention arm and the comparison arm sub-population before the introduction of the 2020 Zambian guidelines (including Burkina Faso control arm)
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2022.
- Background: PubMed 26603917Nagot 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.
- Background: PubMed 33872801Mennecier 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.
- Derived from this study: PubMed 38484756Kankasa 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe Van de Perre, MD, PhD principal investigator
Institut National de la Santé Et de la Recherche Médicale, France
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lamivudine Oral Solution in people with HIV-1, run by ANRS, Emerging Infectious Diseases at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Zambia, Burkina Faso. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevention of HIV-1 transmission from HIV-1-positive mothers to their breastfeeding children (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03870438, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2022.