Guidance from WHO supports exclusive breastfeeding for infants younger than 6 months, with continued breastfeeding accompanied by appropriate complementary foods until age 2 years or older. Substantial overlap exists between countries where breastfeeding typically extends for multiple years and those countries most affected by HIV. In 2020, approximately 35 000 infant HIV acquisitions occurred as a result of maternal HIV newly acquired during pregnancy or breastfeeding. Multiple large, randomised, placebo-controlled trials have generated evidence to support efficacy of both oral tenofovir-based pre-exposure prophylaxis (PrEP) and dapivirine vaginal rings (DVRs). Results from meta-analyses of placebo-controlled trials show a 51% reduction in the risk of acquiring HIV with oral PrEP compared with placebo; some studies have noted more than 90% efficacy with daily adherence, although substantial variation has been noted across study populations. In clinical trials, via an intention-to-treat analysis, the DVR was noted to be about 30% efficacious at preventing HIV infection. Additional modelling has suggested effectiveness of approximately 50% with consistent use, based on data from subsequent open-label studies. To date, WHO recommends oral PrEP containing tenofovir disoproxil fumarate for pregnant and lactating individuals who are at substantial risk of HIV infection and recognises the increased risk of HIV acquisition in the postnatal period. However, national guidelines and local regulatory approvals for biomedical HIV prevention products typically exclude breastfeeding individuals when lactation-specific safety data are absent.
Consistent with language used in the 2023 Lancet Series on Breastfeeding, we use the terms women and breastfeeding throughout this manuscript for brevity and because most people who breastfeed identify as women; we recognise that not all people who breastfeed or chestfeed identify as women.
The DVR contains 25 mg of dapivirine (a non-nucleoside reverse transcriptase inhibitor) dispersed in a silicone elastomer. In 2020, the European Medicines Agency announced a positive opinion on DVR use for HIV prevention. In 2021, WHO recommended the DVR as an additional prevention choice for individuals at substantial risk of HIV infection as part of combination prevention approaches, on the basis of data from efficacy and open-label extension studies of DVR use. However, insufficient data are available to understand the safety of DVR use during breastfeeding. One previous study, Microbicide Trials Network (MTN)-029/IPM 039, assessed DVR use among lactating individuals whose infants were already weaned. Results showed a favourable safety profile and minimal drug transfer to breastmilk (<1 ng/mL, median 676 pg/mL).
As part of a portfolio evaluating DVR safety across the life course, the MTN conducted the MTN-043 trial to evaluate product safety, drug quantification, and adherence associated with use of DVR and oral PrEP in breastfeeding mother–infant pairs; the trial was not designed to estimate product efficacy.
