Antiretroviral concentrations in breast-feeding infants of women in Botswana receiving antiretroviral treatment.
BACKGROUND
The magnitude of infant antiretroviral (ARV) exposure from breast milk is unknown.


METHODS
We measured concentrations of nevirapine, lamivudine, and zidovudine in serum and whole breast milk from human immunodeficiency virus type 1 (HIV-1)-infected women in Botswana receiving ARV treatment and serum from their uninfected, breast-feeding infants.


RESULTS
Twenty mother-infant pairs were enrolled. Maternal serum concentrations of nevirapine were high (median, 9534 ng/mL at a median of 4 h after nevirapine ingestion). Median breast-milk concentrations of nevirapine, lamivudine, and zidovudine were 0.67, 3.34, and 3.21 times, respectively, those in maternal serum. The median infant serum concentration of nevirapine was 971 ng/mL, at least 40 times the 50% inhibitory concentration and similar to peak concentrations after a single 2-mg/kg dose of nevirapine. The median infant serum concentration of lamivudine was 28 ng/mL, and the median infant serum concentration of zidovudine was 123 ng/mL, but infants were also receiving zidovudine prophylaxis.


CONCLUSIONS
HIV-1 inhibitory concentrations of nevirapine are achieved in breast-feeding infants of mothers receiving these ARVs, exposing infants to the potential for beneficial and adverse effects of nevirapine ingestion. Further study is needed to understand the impact of maternal ARV treatment on breast-feeding HIV-1 transmission, infant toxicity, and HIV-1 resistance mutations among infected infants.
Shapiro
Roger L
RL
Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. rshapiro@bidmc.harvard.edu
Holland
Diane T
DT
Capparelli
Edmund
E
Lockman
Shahin
S
Thior
Ibou
I
Wester
Carolyn
C
Stevens
Lisa
L
Peter
Trevor
T
Essex
Max
M
Connor
James D
JD
Mirochnick
Mark
M
D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001902:Botswana; D001942:Breast Feeding; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D007774:Lactation / Q000378:metabolism*; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008895:Milk, Human; D019829:Nevirapine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine