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. 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. Because there is little published experience with stavudine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
One study measured stavudine in breastmilk samples from nursing mothers who had been randomized to receive the drug as part of a clinical trial to evaluate maternal to child transmission of HIV infection. The dosages, dosage regimens and time of breastmilk sample collection times were not reported. The stavudine milk to plasma ratio was found to be 1.73 in 2 patients.
Fifty-two mothers who were taking stavudine either 30 mg (<60 kg) or 40 mg (>60 kg) twice daily had milk samples analyzed for stavudine. Exact timing of the previous dose was not available. Stavudine was detectable in 44 samples of whole milk and 45 samples of skim milk. The median stavudine concentrations were 151 mcg/L in whole milk and 190 mcg/L in skim milk. The average infant intake of stavudine via breastmilk was estimated to be 22.7 mcg/kg daily.
Twenty-eight mothers who were receiving stavudine 30 mg twice daily as part of a combination antiretroviral regimen provided a total of 93 milk samples at birth, 1 month, 3 months and/or 6 months postpartum. Milk samples were collected at a median of 4.5 hours (range 3.5 to 6 hours) after the previous dose. The median breastmilk stavudine concentration was 105 mcg/L (range 34 to 117 mcg/L).
Four mothers received prophylaxis with stavudine, nevirapine and lamivudine (doses not specified) beginning at week 25 of gestation until 6 months postpartum. Blood samples taken at unspecified times failed to detect (<5 mcg/L) stavudine in 8 infant blood samples.
Fifty-two infants whose mothers who were taking stavudine either 30 mg (<60 kg) or 40 mg (>60 kg) twice daily had blood samples analyzed for stavudine. Exact timing of the mothers' previous dose was not available. Stavudine was undetectable (<5 mcg/L) in all but 7 of the infants with an estimated stavudine intake from milk of 22.7 mcg/kg daily. In the 7 infants who had detectable serum concentrations, all had serum concentrations less than 10 mcg/L and their median serum concentration was 5% (range 1 to 15%) of their mothers' serum concentration.
Breastfed infants of 28 mothers who were receiving stavudine 30 mg twice daily as part of a combination antiretroviral regimen had a total of 30 blood samples analyzed at 1 month, 3 months and/or 6 months postpartum. Samples were collected at a median of 4.5 hours (range 3.5 to 6 hours) after the previous maternal dose and a median of 30 minutes (range 20 to 60 minutes) after the previous nursing. The infants' stavudine plasma concentrations ranged from 0 to 2.5 mcg/L, which was a median of 4% (range 0 to 8%) of the maternal serum concentration.
Effects in Breastfed Infants:
Relevant published information was not found as of the revision date.
Possible Effects on Lactation:
Some case reports and in vitro studies have suggested that proteaseinhibitorsmight cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. One case series found an incidence of gynecomastia of 2.4 cases per person annually among men receiving highly active antiretroviral therapy; 70% of the affected patients were taking stavudine. Gynecomastia was unilateral initially, but progressed to bilateral in 53% of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. 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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