An innovative and integrated intervention package delivered through the health system could protect infants from HIV

12 March 2024

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 11 March 2024.

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.

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.

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. 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. 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.

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.

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.