An innovative and integrated intervention package delivered through the health system could protect infants from HIV
Published on 12 March 2024
The essential
Paediatric HIV infections remain unacceptably high, with UNAIDS estimating 130,000 new cases in 2022, most of which occur during breastfeeding. The widespread implementation of universal HIV testing during pregnancy and immediate maternal antiretroviral therapy (ART) over the past decade has significantly reduced new paediatric HIV infections but has not eliminated them. To improve prevention of postnatal HIV transmission, the PROMISE consortium of researchers from University Teaching Hospital (Zambia), Centre Muraz (Burkina Faso), University of Bergen (Norway) and University of Montpellier and Inserm (France) has evaluated an innovative strategy combining existing tools, including infant screening and maternal viral load monitoring using point-of-care tests, and extended postnatal prophylaxis. The results of this study, funded by the European & Developing Countries Clinical Trials Partnership (EDCTP) and sponsored by ANRS MIE, were published in the Lancet on March 11, 2024.
Why this study?
A substantial proportion of mothers living with HIV have unsuccessful ART, defined by an unsuppressed viral load (i.e. ≥ 1000 cp/mL) during the postnatal period. The PROMISE consortium has shown previously that infant postnatal prophylaxis, using nevirapine or lamivudine, is effective in preventing transmission when mothers were not on ART (ANRS 12174 trial, Nagot N. et al, Lancet 2016). However, the added value of this prophylaxis, over and above maternal ART, in reducing postnatal transmission, is not known. Given that the risk of transmission remains throughout the breastfeeding period, extending prophylaxis beyond the current 6 to 12 weeks, maximum 24 weeks, to cover this period of HIV exposition (i.e., breastfeeding) could be important. By targeting extended prophylaxis at those infants at high-risk, such as those breastfed by a mother with unsuccessful ART, this will maximise the benefits of the available, safe infant prophylaxis whilst minimising any potential low-level or delayed toxicity for infants. Furthermore, the use of point-of-care molecular tests for measuring maternal HIV viral load can provide rapid results to guide infant prophylaxis compared to the slower analysis of existing molecular biology assays performed in central laboratories.
How was the study conducted?
The PROMISE team, therefore, designed an intervention package to apply the best available technologies at the most appropriate timing in the health system. This intervention was evaluated in the PROMISE-EPI randomised controlled trial conducted in Burkina Faso and Zambia, where point-of-care viral load testing together with extended infant prophylaxis using lamivudine was implemented at the second immunisation visit, when there is near complete attendance by mothers and their babies. At this visit, the HIV status of mothers was reassessed and, for mothers with HIV, the status of their infant. The check of the HIV status of mothers was repeated at six months. If the mother’s viral load was too high) at either the second immunization visit or at 6 months, lamivudine oral suspension was prescribed to the infant until the end of breastfeeding. The effect of the intervention was evaluated among HIV-infected mothers and their uninfected infants on the proportion of children with HIV at 12 months by comparing this integrated intervention package against the current national guidelines (derived from WHO recommendations) which recommend 6 to 12 weeks infant prophylaxis from birth, using either nevirapine (Burkina Faso) or a 3-drug combination (Zambia).
What are the main results?
Between December 2019 and September 2021, 34,054 mothers (25,093 in Burkina Faso and 8,961 in Zambia) were screened for HIV at the second immunisation visit and 1,526 (201 in Burkina Faso and 1,491 in Zambia) out of 1,692 HIV-1 infected mothers were enrolled in the study. The mothers had a median age of 30.6 years, 98.4% were receiving ART and 11.5% had a viral load ≥ 1000 cp/mL. By the end of the study, only one infant in the intervention group became infected with HIV compared to six infants infected in the control arm, equating to a transmission incidence rate of 0.19% in the intervention arm and 1.16% in the control arm. The mean duration of very high risk of transmission (defined as maternal viral load >1000 copies/mL and no infant prophylaxis) was more than 10 times lower in the intervention group than in the control group, thus supporting the effectiveness of the intervention. This important difference in HIV incidence did not reach statistical significance though, mainly because the closures of some study sites due to the COVID-19 epidemic prevented them from enrolling as many infants as initially planned. Importantly, there was no difference in serious adverse events between both groups, attesting to the safety of this intervention.
Conclusion
These results strongly suggest that HIV transmission through breastfeeding can be reduced almost to zero with a combination of existing tools, including infant testing and maternal viral load monitoring with point of care assays, and extended prophylaxis. The findings also show that single-drug prophylaxis with lamivudine, in addition to maternal ART, can reduce postnatal transmission to HIV elimination levels. The extension of this prophylaxis to 12 months among infants with the highest risk of infection may be pivotal in the results. By preventing almost all postnatal HIV transmission using existing tools employed at the right time in the health system, paediatric HIV elimination is within reach. These platforms are widely available in Africa, through both tuberculosis and HIV control programs for early infant diagnosis. Lamivudine syrup is cheap and readily available from generic manufacturers. Although our study did not include rural sites, where the feasibility of this intervention should be evaluated, this innovative strategy proved effective in health systems and countries as diverse as Zambia and Burkina Faso, supporting its generalization to other sub-Saharan African countries.
Reference
The PROMISE-EPI study (grant number RIA2016MC-1617) is part of the EDCTP2 programme supported by the European Union with funding from UK National Institute for Health and Care Research (NIHR). NIHR is funded by the Department of Health and Social Care. The NIHR Global Health Research portfolio supports high-quality applied health research for the direct and primary benefit of people in low- and middle-income countries, using international development funding from the UK Government.
About
About ANRS MIE and its international network:
ANRS Emerging Infectious Diseases, created on 1 January 2021, is an autonomous agency of Inserm, headed by Professor Yazdan Yazdanpanah. Its remit is to lead, evaluate, coordinate and fund research into HIV/AIDS, viral hepatitis, sexually transmitted infections, tuberculosis and emerging and re-emerging infectious diseases (in particular emerging respiratory infections – including Covid-19 – viral hemorrhagic fevers and arboviruses). The agency acts both nationally and internationally.
Zambia and Burkina Faso are countries with which the ANRS MIE has maintained close relations for many years, particularly through its International Network, within which partnerships have been set up between stakeholders from France and from low- and middle-income countries. In Burkina Faso, collaboration has been centered on the Muraz Centre, national research institution for health and a part of the Institute of Public Health (INSP) in Ouagadougou since it was set up in 2001. In Zambia, the PROMISE-EPI study is the fruit of collaboration between Zambian researchers and French researchers from UMR 1058-PCCEI in Montpellier, which began more than 20 years ago through the PROMISE Consortium dedicated to maternal and child health. This collaboration is currently continuing with the PROMISE-Zero study, funded by the Global Health EDCTP3 programme, with a partnership between UTH (University Teaching Hospital) and ANRS MIE for sponsorship.
Find out more about the ANRS MIE international network and partnerships
About Montpellier University
With over 52,000 students to its 17 faculties, schools and institutes (plus one Component Plant: ENSCM), the University of Montpellier (UM) covers the main fields of study: agriculture, food, law and social sciences, economics, management, education, technology, engineering, health and science. In close collaboration with the socio-economic world, UM provides students with lifelong training and gives them the skills they need to build their careers. In a world where technology is constantly evolving, studying at the UM is an opportunity for everyone to learn about the jobs of the future and to move into the workplace.
From space exploration and robotics to ecological engineering and chronic diseases, UM researchers are inventing tomorrow’s solutions for humankind and the environment. The UM is committed to promoting its cutting-edge research by forging close links with local industry, particularly in the biomedical and new technologies sectors. Dynamic research, conducted in close collaboration with research organizations and benefiting from high-level technological platforms to meet the needs of 21st century society. The University of Montpellier is one of the world’s leading universities. UM tops international rankings: in the world’s top 200 in the Shanghai rankings and the second most innovative French university in Reuters’ rankings.
About EDCTP
The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 15 European and 28 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and post-registration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. For more information, please visit www.edctp.org
About Inserm
Founded in 1964, Inserm is a public scientific and technological institute, which operates under the joint authority of the French Ministries of Health and Research. The institute is dedicated to biomedical research and human health, and is involved in the entire range of activities from the laboratory to the patient’s bedside. It also collaborates with the most prestigious research institutions in the world that are committed to scientific challenges and progress in these fields.