Written by: Anna Petherick, Ph.D. | Issue # 58 | 2017
- The World Health Organization warns women against taking HIV prophylactic drugs while breastfeeding, due to the potential for side effects associated with these drugs to affect infants.
- The WHO recommendation was made because it was not known whether such drugs find their way into human milk in significant concentrations.
- Researchers have now measured the exact levels of two HIV prophylactics in human milk: tenofovir and emtricitabine, which are often taken together.
- Tenofovir and emtricitabine are present in such extremely low concentrations that it is impossible for side-effects to pose a risk to infants who consume milk from women taking them.
The World Health Organization considers someone with more than a 3% chance of contracting HIV in the next year to have a “substantial” risk of infection. This is important because it is the cut-off for which the WHO recommends taking anti-retroviral drugs, like tenofovir, to reduce the odds of infection. Breastfeeding women in sub-Saharan Africa easily meet this risk threshold . But medical professionals are discouraged from offering the drug to these women because of WHO warning labels about potential adverse reactions in nursing infants. That advice may now change, paving the way for many more at-risk women to receive HIV prophylaxis. A new study shows that when infants consume human milk from a woman taking tenofovir in combination with emtricitabine, they are exposed to extremely low levels of either drug. Therefore, the infants’ likelihood of experiencing adverse reactions is virtually non-existent .
The usefulness of tenofovir to prevent HIV infection has been supported by many studies. A trial of intravenous drug users in Thailand, for example, recorded a 48.9% lower incidence of infection among participants who took it instead of a placebo . A study of heterosexual people in Botswana found that tenofovir taken alongside emtricitabine (a combination given the acronym, FTC-TDF) was 62.2% effective at preventing HIV infection . But these trials offered no insight into whether lactating women could take the drug without harming their breastfeeding offspring. This is because lactating women were excluded from the trials. Indeed, women were dropped from the trials as soon as they became pregnant .
As a result, there was a gap in medical knowledge about the drugs’ usefulness. Without proof either way as to whether FTC-TDF circulating in a woman’s bloodstream could get into her milk—and thus whether or not the drugs might affect the tiny body of a breastfeeding infant—the World Health Organization’s official advice was to err on the side of caution.
Kenneth Mugwanya of University of Washington, Seattle, was all too aware of how many women’s lives might be saved with more data. If indeed these drugs present minimal risk to nursing infants, women could continue to protect themselves against HIV while they breastfed. Prophylactic drugs are especially important for women in the fight against HIV/AIDS because individuals have full autonomy over the decision to protect themselves, which is not the case with some other methods, such as use of condoms, for protection against its sexual transmission. So Mugwanya and his colleagues set about designing a lactation trial.
The team, drawn from Uganda, Kenya, and the United States, managed to recruit 50 HIV-free women, who, along with each infant’s father, consented to their infants being enrolled in the trial. These women were then given FTC-TDF for 10 days in a row. During this period, they breastfed their infants as usual.
The researchers sought to find out the extent to which both tenofovir and emtricitabine were excreted by the women’s bodies into their milk. Using a technique called liquid chromatography-tandem mass spectrometry, the team measured the amounts of both drugs circulating in the mothers’ bloodstreams, the concentrations found in their milk, and how much these concentrations varied throughout the day. The same measurement technique was then applied to a blood sample drawn from the breastfeeding infants after their mothers had taken FTC-TDF for a week.
The results were surprisingly reassuring. Infants in the trial received about 12,500 times less tenofovir via their mother’s milk than the dose of this drug that has been proposed for prophylatic use in infants whose mothers are HIV positive. The amount of emtricitabine in human milk was also very low—more than 200 times less than the dose proposed for an infant prophylatic.
Therefore, both drugs were well within the medical community’s rule-of-thumb for when a lactating woman can continue to take a medication without worrying about her child experiencing associated side effects: the concentration was less than 10% of the weight-adjusted recommended therapeutic dose of the drug for infants . Tenofovir could not even be detected in 94% of the infants’ blood samples, and the levels of emtricitabine in the infants’ blood were also extremely low. Importantly, there was little variation in blood concentrations of the drug among the infants, nor among the milks produced by their mothers.
Mugwanya and his team have provided the evidence that a change is needed in the WHO’s official advice. HIV-negative women at high risk of contracting the virus should not stop taking their prophylatic drugs because they are breastfeeding. This finding is hugely important given that 71% of new HIV infections in sub-Saharan Africa are among women and girls, and HIV prevalence in the region is now eight times higher among teenage girls from 15–19 years old, than it is among males of the same age .
In the past year, both Kenya  and South Africa  have approved the prophylactic use of FTC-TDF. As those countries roll out these new public health policies, they should ensure that medical professionals are fully aware of the findings of Mugwanya et al. .
1. Mofenson, L. M. 2016. Tenofovir pre-exposure prophylaxis for pregnant and breastfeeding women at risk of HIV infection: the time is now. PLoS Med 13(9): e1002133.
2. Mugwanya, K. K., et al. 2016. Pre-exposure prophylaxis use by breastfeeding HIV-uninfected women: a prospective short-term study of antiretroviral excretion in breast milk and infant absorption. PLoS Med 13(9): e1002132.
3. Choopanya, K., et al. 2013. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 381(9883): 2083-2090.
4. Thigpen, M. C., et al. 2012. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 367(5): 423-434.
5. Ito, S. 2000. Drug therapy for breast-feeding women. N Engl J Med 343(2): 118-126.
6. Gilead Statement on the approval of FTC-TDF as a prophylactic in Kenya. 23 December 2015. https://xa.yimg.com/kq/groups/17854090/2023799735/name/kenya_prep_approval_statement_‹_final.pdf. Accessed November 21, 2016.
7. South Africa Medicines Control Council statement of the approval of FTC-TDF as a prophylatic. 3 December 2015. http://www.mccza.com/documents/2e4b3a5310.11_Media_release_ARV_FDC_PrEP_Nov15_v1.pdf Accessed November 21, 2016.