In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, exclusive breastfeeding for 6 months is recommended for HIV-infected mothers to reduce the risk of HIV transmission from the mother to the infant compared with mixed feeding. In these settings, abrupt weaning at 4 months does not reduce the risk of HIV transmission or produce an overall health benefit compared to continued breastfeeding, and increases the risk of infant death in HIV-infected infants. Nelfinavir is often used as part of a regimen that decreases mother-to-child transmission of HIV and is generally well tolerated by the breastfed infant. Extended antiretroviral prophylaxis in breastfed infants with antiretroviral drugs appears to reduce the rate of HIV transmission during breastfeeding by about half, but the optimal regimen and duration of prophylaxis has not yet been defined. The infants who do become HIV infected during breastfeeding by mothers receiving a highly active antiretroviral therapy (HAART) regimen that includes nelfinavir are often infected with multi-class resistant HIV; however, levels of nelfinavir in the infant are very low and resistance to nelfinavir usually does not develop. Breastfed infants whose mothers receive HAART have higher rates of neutropenia during the first month and severe anemia during the first 6 months of life.
Five women were receiving nelfinavir 1250 mg twice daily as part of a highly-active antiretroviral combination regimen. During the first 5 days postpartum milk was collected just before and 2 hours after the dose of nelfinavir. Breastmilk nelfinavir concentrations ranged between 6 and 24% of the maternal serum concentration. The M8 metabolite was not detectable in milk. Further details on the timing, or actual breastmilk concentrations were not provided.
Twenty-six samples of breastmilk and maternal serum were obtained at 6, 12 and 24 weeks postpartum from mothers taking nelfinavir as part of a combination of antiretrovirals. The nelfinavir dosage the mothers were taking was not stated in the abstract. The median breastmilk concentrations of nelfinavir were 49 mcg/L at a median of 14 hours after the last dose at 6 weeks postpartum (10 samples), 51 mcg/L at a median of 14 hours after the last dose at 12 weeks postpartum (7 samples), and 184 mcg/L at a median of 16 hours after the last dose at 24 weeks postpartum (9 samples). Median milk concentrations were 8% (interquartile range 4 to 14%) of maternal plasma concentrations. In a related study by the same authors, the nelfinavir milk to plasma ratio was found to be 0.21 in 29 patients.
Twenty-six breastfeeding Kenyan mothers were receiving oral nelfinavir 1.25 grams twice daily in addition to zidovudine and lamivudine for HIV infection. Blood and breastmilk samples were collected at delivery, and at 2, 6, 14, and 24 weeks postpartum at various times after the previous dose of nelfinavir. The 104 breastmilk samples were analyzed for nelfinavir and its active metabolite, hydroxyl-t-butylamidenelfinavir (M8). Median breastmilk nelfinavir concentrations were 83 mcg/L at birth, 358 mcg/L at 2 weeks, 286 mcg/L at 6 weeks, 233 mcg/L at 14 weeks and 180 mcg/L at 24 weeks postpartum. The M8 metabolite was undetectable (<10 mcg/L) in most samples; the highest concentrations found at any time was 32 mcg/L. Nelfinavir levels in breastmilk tended to drop during the dosing interval but M8 levels were relatively stable.
The infants of postpartum mothers taking nelfinavir as part of a combination of antiretrovirals had undetectable serum nelfinavir concentrations by HPLC/MS analysis. The nelfinavir dosage the mothers were taking and times of infant plasma sampling were not stated in the abstract. Nelfinavir was not detectable in infant plasma at 6, 12 or 24 weeks of age.
Twenty-six breastfeeding Kenyan mothers were receiving oral nelfinavir 1.25 grams twice daily in addition to zidovudine and lamivudine for HIV infection. Infant blood samples were obtained at various times between 2 and 24 weeks postpartum. Nelfinavir and M8 concentration were undetectable (<10 mcg/L) for 20 of the 28 infant blood samples. The highest concentrations detected were 30 mcg/L for nelfinavir and 32 mcg/L for M8 which are less than the MIC for the HIV virus.
Effects in Breastfed Infants:
Relevant published information was not found as of the revision date.
Possible Effects on Lactation:
Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that proteaseinhibitorsmight cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed.
The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
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