Research is urgently needed to provide clear recommendations on breastfeeding to mothers with HIV who have an undetectable viral load on antiretroviral treatment, a group of researchers led by Catriona Wiatt at the department of molecular and clinical pharmacology, University of Liverpool, Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda and Royal Liverpool University Hospital, say.
They say that: “There is insufficient evidence to state that U=U (undetectable equals untransmittable) in the context of breastfeeding”. Although the risk of transmission is probably small if women have suppressed viral load, the authors highlight a number of research questions that still need to be addressed in order to give evidence-based advice.
In resource-limited settings, the World Health Organisation recommends that women with HIV should breastfeed if formula feeding is not safe and feasible and that mothers should receive antiretroviral therapy and infants should receive antiretroviral prophylaxis.
In high-income settings, guidelines have discouraged breastfeeding in women on antiretroviral treatment. However, recent guideline updates by the British HIV Association (BHIVA), the European AIDS Clinical Society and the US Department of Health and Human Services each acknowledge that women with undetectable viral loads may choose to breastfeed, and if they do so, regular viral load and adherence monitoring should take place to minimise the risk of transmission.
But the authors of the review say there is still a lack of evidence to determine how women who breastfeed should be monitored and what risks might remain, despite an undetectable viral load. The authors say that several important research questions still need to be answered to give women the fullest possible information about the risks of breastfeeding, and to determine what package of monitoring and support is necessary during the breastfeeding period.
They highlight questions that still need to be answered.
Several studies have shown that women can have detectable HIV in breast milk even when they have undetectable HIV in plasma. Investigators on the Breastfeeding, Antiretrovirals and Nutrition (BAN) study concluded that maintaining a plasma viral load below 100 copies/ml may prevent breast milk transmission, based on the observation that all mothers who transmitted HIV during breastfeeding in that study had at least one plasma viral load measurement above 100 copies/ml. However, the Mma Bana study in Botswana identified two cases of transmission that probably occurred during the breastfeeding period and where each mother had a plasma viral load below 50 copies/ml both one month and three months after delivery (infant infection was detected in each case around 90 days after delivery). In one case the mother reported adherence difficulties.
Furthermore, one case has been documented in Malawi where HIV was transmitted through breastfeeding even though the mother had an undetectable viral load (< 37 copies/ml) in both plasma and breast milk.
A mathematical modelling exercise led by UNAIDS, based on all available data from clinical trials and observational cohorts up to 2012, estimated that there was a 0.16% (approximately one in 750) risk of HIV transmission for every month of breastfeeding if the mother had already started antiretroviral treatment prior to delivery.
These findings show that the risk of transmission is small but cannot be ruled out. The researchers recommend the establishment of an international registry that will record the outcomes of all breastfed infants of mothers with HIV. As well as looking at drug safety in infants, a registry would provide detailed information on any cases of transmission that might occur and improve estimates of the risk of transmission. The persisting risk of transmission through breast milk despite viral suppression in plasma is probably a consequence of cell-associated virus in breast milk, experts have concluded.
HIV may be cell-free or it may be cell-associated, that is, contained within an immune system cell such as a CD4 lymphocyte in the form of viral DNA. Breast milk contains several types of cells potentially infected with HIV. These cells include long-lived latently infected CD4 cells containing pro-viral DNA that is not replicating and so is not susceptible to antiretroviral drugs.
The researchers say that more research is needed to establish whether long-term antiretroviral treatment prior to breastfeeding reduces levels of cell-associated virus in breast milk.
The BHIVA recommends that women who are breastfeeding while on antiretroviral treatment should attend their clinic once a month for a viral load test for themselves and their infant. US guidelines indicate testing every one to two months.
Although draft BHIVA guidelines recommend against breastfeeding, they acknowledge that some women will choose to do so and that it is better that women can be open about this choice and receive support from their clinic to minimise the risk of transmission.
The BHIVA draft guidelines recommend a harm reduction approach: minimise the amount of time that breastfeeding takes place, stop breastfeeding if the infant has any gastrointestinal symptoms or if the mother has mastitis or a breast infection, and test viral load in mother and baby once a month during breastfeeding.
BHIVA guidelines emphasise that “Women who breastfeed with a known detectable HIV viral load should be referred to social care as they are putting their infant at significant risk of HIV infection.”
Summary
Can the campaign Undetectable=Untransmittable (U=U), established for the sexual transmission of HIV, be applied to the transmission of HIV through breastfeeding? European AIDS Clinical Society and, to some extent, American guidelines now state that mothers with HIV who wish to breastfeed should be supported, with increased clinical and virological monitoring. This Viewpoint summarises existing evidence on transmission of HIV through breastfeeding, differences in HIV dynamics and viral load between breastmilk and plasma, and the effects of antiretroviral therapy on infants. At present, insufficient evidence exists to make clear recommendations for the required frequency of clinical and virological monitoring for mother and infant in a breastfeeding relationship or for the action to be taken in the event of viral rebound. We propose a roadmap for collaborative research to provide the missing evidence required to enable mothers who wish to breastfeed to make a fully informed choice.
Authors
Catriona Waitt, Nicola Low, Philippe Van de Perre, Fiona Lyons, Mona Loutfy, Karoline Aebi-Popp
[link url="http://www.aidsmap.com/Does-UU-for-breastfeeding-mothers-and-infants-Researchers-highlight-unanswered-questions/page/3305996/"]Aidsmap material[/link]
[link url="https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(18)30098-5/fulltext"]The Lancet HIV abstract summary[/link]