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Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.
As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).
The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.
Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.
Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.
In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.
Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.
“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.
“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.
This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.
On Twitter @jessnicolecraig
The research article by Dr. Mugwanya and his colleagues in PLOS Medicine significantly contributes to the accumulating safety data for PrEP in breastfeeding women. This documents a prospective study of daily tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) in 50 HIV-uninfected breastfeeding women between 1-24 weeks postpartum; the drug combination was provided to women for 10 consecutive days and then discontinued. In infant plasma, tenofovir was below the limit of detection in 46 (94%) of 49 samples; 47 of 49 (96%) infant samples had detectable FTC. Based on breast milk concentrations, breastfeeding infants would have exposures to TDF 12,500-fold lower and to FTC 200-fold lower than those achieved with pediatric therapeutic dosing (less than 0.01% and 0.5% of therapeutic dose, respectively).
These data confirm and extend other studies that have reported very-low concentrations of tenofovir detectable in breast milk and strongly suggest that TDF and TDF/FTC can safely be given to breastfeeding women without putting their infants at risk of adverse effects.
Although the World Health Organization calls for further research, current WHO guidelines are permissive of the use of PrEP during pregnancy and breastfeeding, noting growing evidence for safety from maternal HIV and hepatitis B virus studies. WHO is currently reviewing data on safety of PrEP in pregnancy and lactation and will provide more detailed guidance in the near future. Although it will be important to collect additional safety data, the weight of the existing evidence does not support further delay in implementing TDF PrEP for pregnant and breastfeeding women at high risk of HIV acquisition. Those women on PrEP who become pregnant or are lactating should not have to stop an effective HIV prevention intervention.
Lynne M. Mofenson, MD, is a senior HIV technical adviser at the Elizabeth Glaser Pediatric AIDS Foundation. Dr. Mofenson had no relevant disclosures to report. These comments are adapted from her perspective accompanying the study (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002133).
The research article by Dr. Mugwanya and his colleagues in PLOS Medicine significantly contributes to the accumulating safety data for PrEP in breastfeeding women. This documents a prospective study of daily tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) in 50 HIV-uninfected breastfeeding women between 1-24 weeks postpartum; the drug combination was provided to women for 10 consecutive days and then discontinued. In infant plasma, tenofovir was below the limit of detection in 46 (94%) of 49 samples; 47 of 49 (96%) infant samples had detectable FTC. Based on breast milk concentrations, breastfeeding infants would have exposures to TDF 12,500-fold lower and to FTC 200-fold lower than those achieved with pediatric therapeutic dosing (less than 0.01% and 0.5% of therapeutic dose, respectively).
These data confirm and extend other studies that have reported very-low concentrations of tenofovir detectable in breast milk and strongly suggest that TDF and TDF/FTC can safely be given to breastfeeding women without putting their infants at risk of adverse effects.
Although the World Health Organization calls for further research, current WHO guidelines are permissive of the use of PrEP during pregnancy and breastfeeding, noting growing evidence for safety from maternal HIV and hepatitis B virus studies. WHO is currently reviewing data on safety of PrEP in pregnancy and lactation and will provide more detailed guidance in the near future. Although it will be important to collect additional safety data, the weight of the existing evidence does not support further delay in implementing TDF PrEP for pregnant and breastfeeding women at high risk of HIV acquisition. Those women on PrEP who become pregnant or are lactating should not have to stop an effective HIV prevention intervention.
Lynne M. Mofenson, MD, is a senior HIV technical adviser at the Elizabeth Glaser Pediatric AIDS Foundation. Dr. Mofenson had no relevant disclosures to report. These comments are adapted from her perspective accompanying the study (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002133).
The research article by Dr. Mugwanya and his colleagues in PLOS Medicine significantly contributes to the accumulating safety data for PrEP in breastfeeding women. This documents a prospective study of daily tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) in 50 HIV-uninfected breastfeeding women between 1-24 weeks postpartum; the drug combination was provided to women for 10 consecutive days and then discontinued. In infant plasma, tenofovir was below the limit of detection in 46 (94%) of 49 samples; 47 of 49 (96%) infant samples had detectable FTC. Based on breast milk concentrations, breastfeeding infants would have exposures to TDF 12,500-fold lower and to FTC 200-fold lower than those achieved with pediatric therapeutic dosing (less than 0.01% and 0.5% of therapeutic dose, respectively).
These data confirm and extend other studies that have reported very-low concentrations of tenofovir detectable in breast milk and strongly suggest that TDF and TDF/FTC can safely be given to breastfeeding women without putting their infants at risk of adverse effects.
Although the World Health Organization calls for further research, current WHO guidelines are permissive of the use of PrEP during pregnancy and breastfeeding, noting growing evidence for safety from maternal HIV and hepatitis B virus studies. WHO is currently reviewing data on safety of PrEP in pregnancy and lactation and will provide more detailed guidance in the near future. Although it will be important to collect additional safety data, the weight of the existing evidence does not support further delay in implementing TDF PrEP for pregnant and breastfeeding women at high risk of HIV acquisition. Those women on PrEP who become pregnant or are lactating should not have to stop an effective HIV prevention intervention.
Lynne M. Mofenson, MD, is a senior HIV technical adviser at the Elizabeth Glaser Pediatric AIDS Foundation. Dr. Mofenson had no relevant disclosures to report. These comments are adapted from her perspective accompanying the study (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002133).
Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.
As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).
The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.
Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.
Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.
In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.
Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.
“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.
“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.
This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.
On Twitter @jessnicolecraig
Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.
As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).
The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.
Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.
Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.
In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.
Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.
“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.
“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.
This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.
On Twitter @jessnicolecraig
FROM PLOS MEDICINE
Key clinical point: PrEP can be used safely in HIV-uninfected women who are breastfeeding.
Major finding: Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. While emtricitabine was detectable in 47 of 49 (96%) infant plasma samples, median concentration was low (13.2 ng/mL).
Data source: A prospective short-term study of 50 mother-infant pairs in Kenya and Uganda.
Disclosures: This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.
