Breastfeeding by Women with HIV Infection

Pre-Exposure Prophylaxis in Couples with Differing HIV Statuses

For use in HIV-negative women in a relationship with an HIV-positive partner. The fixed-dose combination of tenofovir disoproxil fumarate (TDF) and emtricitabine taken once daily is currently approved by the U.S. Food and Drug Administration for use as pre-exposure prophylaxis. This single tablet combination product is acceptable to use during breastfeeding. ¹ Not mentioned in the U.S. guidelines is the newer Food and Drug Administration-approved combination therapy consisting of emtricitabine and tenofovir alafenamide. A recent abstract reported tenofovir levels in milk to be below the lower limit of quantitation with this form of tenofovir. ⁶

Women with HIV Taking HIV Suppressive Treatment

The same regimens that are recommended for the treatment of nonpregnant adults are used in pregnant women when sufficient data suggest that appropriate drug exposure is achieved during pregnancy. Clinicians should weigh the risks of adverse effects for women or infants against the benefits of these regimens and recognize that there are often incomplete data on the safety of ART drugs in pregnancy. The same regimens are generally continued during breastfeeding.

The WHO recommends treating pregnant and breastfeeding women with the combination of TDF, lamivudine, and dolutegravir. ⁷ U.S. regimens vary depending on the woman's situation. The preferred regimens for women with no previous ART consist of a “backbone” of two nucleoside reverse transcriptase inhibitors plus a third drug from another drug class. Backbone regimens include abacavir plus lamivudine, TDF plus emtricitabine, or TDF plus lamivudine. The recommended third drug can be an integrase strand transfer inhibitor, either dolutegravir or raltegravir; or a protease inhibitor, either atazanavir or darunavir.

U.S. guidelines state that supporting maternal ART adherence and engagement in care both during pregnancy and throughout breastfeeding consists of:

Documenting consistent viral suppression before delivery and throughout breastfeeding. This can be accomplished by monitoring maternal plasma viral loads every 1–2 months during breastfeeding. Plasma viral loads should also be monitored whenever nonadherence to ART is suspected. If maternal viral load becomes detectable, consult an expert immediately and consider weaning the infant.

Safety of Maternal and Infant Use of ARV Drugs During Breastfeeding

The non-nucleoside reverse transcriptase inhibitors (NNRTIs), nevirapine, efavirenz, and etravirine have been detected in breast milk; however, the levels of these drugs that have been detected in breast milk are lower than those seen in maternal plasma. Among protease inhibitors, lopinavir, nelfinavir, ritonavir, indinavir, and atazanavir have been found in very low concentrations in breast milk, with little to no drug detectable in the blood of the breastfed infant. NNRTIs show more variability than protease inhibitors and NNRTIs. TDF concentrations are very low in breast milk, and the drug is undetectable in the blood of the breastfed infant. Emtricitabine and lamivudine have more accumulation in breast milk and can sometimes be detected in the blood of the breastfed infant (in 19% and 36% of infants, respectively). Data on the transfer of integrase strand transfer inhibitors to breast milk in humans is limited; data do show that dolutegravir is found in breast milk at levels that are ∼3% of those seen in maternal plasma.

In infants, serious adverse events that are associated with the use of ART by breastfeeding mothers appear to be relatively uncommon. In two studies that compared the efficacy of maternal ART (zidovudine-based ART in one study and TDF-based ART in the other) to infant nevirapine prophylaxis with no maternal ART during breastfeeding for prevention of postnatal HIV transmission, no significant differences in adverse events were observed between study arms. One study reported that anemia occurred more frequently among infants who were exposed to zidovudine-based ART during breastfeeding than among infants who were not exposed to ART. An infant who acquires HIV while breastfeeding is at risk for developing ARV drug resistance due to subtherapeutic drug levels in breast milk.

Likewise, the rates of serious adverse events among infants who receive extended ARV prophylaxis are low. In one study, the rate of adverse events in infants receiving 6 months of nevirapine was not significantly different from the rate in infants receiving placebo. A second study that compared two infant ARV prophylaxis regimens (lopinavir/ritonavir versus nevirapine) found no significant difference between the rates of adverse events among infants receiving the two regimens. Studies to date have only examined short-term adverse events, and there is little data on whether there might be long-term consequences of these drug exposures.

Lactation Inhibition

For women who do not breastfeed (as recommended for women with HIV), symptoms related to breast engorgement can be very unpleasant in the days after labor and delivery. Supportive measures, such as using acetaminophen or ibuprofen for pain control, alternating hot and cold compresses on the breasts, or wearing a tight-fitting sports bra, can help relieve symptoms related to breast engorgement. Although pharmacological options for lactation inhibition are not generally used in the United States, recent data suggest cabergoline may be appropriate for some women. Cabergoline is a dopamine agonist that reduces the production of prolactin. Because of its prolonged half-life, a single 1 mg dose of cabergoline given on the first day after delivery can suppress prolactin production for up to 21 days and effectively inhibit milk production. A systematic review and a scoping review assessing the safety and use of cabergoline for postpartum lactation inhibition both reported that side effects are common, but transient, and include dizziness, headache, nausea, and vomiting. However, severe and less common side effects such as postpartum psychosis have been reported. Available data on the safety profile of cabergoline are from small studies that may not have adequately captured the prevalence of serious side effects. Cabergoline is contraindicated for women with hypertension (including pregnancy-induced hypertension, preeclampsia, or eclampsia) or liver disease, and in women being treated with antipsychotics or those who have a history of puerperal psychosis.

Summary

Breastfeeding is discouraged in women with HIV in high-income countries, but this guidance is beginning to be questioned by some. Although transmission of HIV infection to infants is low with appropriate therapy, it is not zero. U.S. guidelines now provide information on how to most safely accomplish breastfeeding in women with HIV.