Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post-partum: results of the BAN Study.
BACKGROUND
An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral and Nutrition (BAN) Study was performed to describe drug exposure and antiviral response.


METHODS
Women using Combivir(®) (zidovudine [ZDV] + lamivudine [3TC]) +Aluvia(®) (lopinavir/ritonavir [LPV/RTV]) were enrolled. Breast milk (BM), mother plasma (MP) and infant plasma (IP) samples were obtained over 6 h after observed dosing at 6, 12 or 24 weeks post-partum for drug concentrations and HIV RNA.


RESULTS
A total of 30 mother/infant pairs (10 each at 6, 12 and 24 weeks post-partum) were enrolled. Relative to MP, BM concentrations of ZDV and 3TC were 35% and 21% higher, respectively, whereas LPV and RTV were 80% lower. Only 3TC was detected in IP with concentrations 96% and 98% lower than MP and BM, respectively. Concentrations in all matrices were similar at 6-24 weeks. The majority (98.3%) of BM concentrations were >HIV(wt) IC50, with one having detectable virus. There was no association between PK parameters and MP or BM HIV RNA.


CONCLUSIONS
ZDV and 3TC concentrated in BM whereas LPV and RTV did not, possibly due to protein binding and drug transporter affinity. Undetectable to low antiretroviral concentrations in IP suggest prevention of transmission while breastfeeding may be due to antiretroviral effects on systemic or BM HIV RNA in the mother. Low IP 3TC exposure may predispose an infected infant to HIV resistance, necessitating testing and treating infants early.
The University of North Carolina, Eshelman School of Pharmacy, Chapel Hill, NC, USA. ahcorbet@email.unc.edu.
Amanda H
AH
Corbett
Dumbani
D
Kayira
Nicole R
NR
White
Nicole L
NL
Davis
Athena P
AP
Kourtis
Charles
C
Chasela
Francis
F
Martinson
Grace
G
Phiri
Bonaface
B
Musisi
Deborah
D
Kamwendo
Michael G
MG
Hudgens
Mina C
MC
Hosseinipour
Julie Ae
JA
Nelson
Sascha R
SR
Ellington
Denise J
DJ
Jamieson
Charles
C
van der Horst
Angela
A
Kashuba
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001942:Breast Feeding; D018791:CD4 Lymphocyte Count; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D008895:Milk, Human; D009035:Mothers; D013997:Time Factors; D019562:Viral Load; D055815:Young Adult
D019380:Anti-HIV Agents