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.
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.
Authors: Cristina M Marazzi; Paola Germano; Giuseppe Liotta; Giovanni Guidotti; Sandra Loureiro; Aurelio da Cruz Gomes; Maria C Valls Blazquez; Pasquale Narciso; Carlo F Perno; Sandro Mancinelli; Annamaria Doro Altan; Karin Nielsen-Saines; Leonardo Palombi Journal: Eur J Pediatr Date: 2007-01-18 Impact factor: 3.183
Authors: Roger L Shapiro; Diane T Holland; Edmund Capparelli; Shahin Lockman; Ibou Thior; Carolyn Wester; Lisa Stevens; Trevor Peter; Max Essex; James D Connor; Mark Mirochnick Journal: J Infect Dis Date: 2005-07-27 Impact factor: 5.226
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Authors: K H Moore; S Shaw; A L Laurent; P Lloyd; B Duncan; D M Morris; M J O'Mara; G E Pakes Journal: J Clin Pharmacol Date: 1999-06 Impact factor: 3.126
Authors: R Nduati; B A Richardson; G John; D Mbori-Ngacha; A Mwatha; J Ndinya-Achola; J Bwayo; F E Onyango; J Kreiss Journal: Lancet Date: 2001-05-26 Impact factor: 79.321
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