***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The safety , pharmacokinetics , and antiretroviral activity of lamivudine alone and in combination with zidovudine was studied in pregnant women infected with human immunodeficiency virus type 1 ( HIV-1 ) and their neonates . Women received the drugs orally from week 38 of pregnancy to 1 week after delivery . Neonate therapy began 12 h after delivery and continued for 1 week . Both treatment regimens were well-tolerated  in women and newborns .  Lamivudine and zidovudine  pharmacokinetics in pregnant women were similar to those in nonpregnant adults . Lamivudine and zidovudine freely crossed the placenta and were secreted in breast milk . Neonatal lamivudine clearance was about half that in pediatric patients ; zidovudine  clearance was consistent with previous reports . HIV-1 RNA could be quantified in 17 of the 20 women . At the onset of labor/delivery , mean virus load had decreased by approximately 1.5 log10 copies/mL in both treatment cohorts . Although not definitive for HIV-1 infection status , all neonates had HIV-1 RNA levels below the limit of quantification at birth and at ages 1 and 2 weeks Analysis of a sub study of the Kisumu breastfeeding trial by Clement Zeh and colleagues reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs Background : The administration of antiretroviral therapy to lactating women could represent a possible strategy to reduce postnatal HIV transmission . In this study , we assessed the effect of antiretroviral treatment on breast milk viral load and determined plasma and breast milk drug concentrations in pregnant women receiving highly active antiretroviral therapy ( HAART ) . Methods : We studied 40 women receiving zidovudine , lamivudine , and nevirapine from 28 weeks of gestation to 1 month postpartum ( group A ) and 40 untreated pregnant women ( group B ) . Blood and breast milk sample s were collected at delivery and 7 days postpartum . Results : Women in group A had received a median of 85 days of therapy before delivery . Median breast milk concentrations of nevirapine , lamivudine , and zidovudine were 0.6 , 1.8 , and 1.1 times , respectively , those in maternal plasma . HIV RNA levels in breast milk were significantly lower in group A than in group B ( median of 2.3 vs. 3.4 log at delivery and 1.9 vs. 3.6 log at day 7 ; P < 0.001 for both comparisons ) . Conclusions : Antiretroviral drugs administered during the last trimester of pregnancy and after delivery reach levels similar to or higher than plasma concentrations in breast milk and can significantly reduce HIV RNA levels . Our data support the potential role of maternal HAART prophylaxis in reducing the risk of breast-feeding-associated transmission The safety , toxicity , and pharmacokinetics of intrapartum and early newborn nevirapine were evaluated in 17 human immunodeficiency virus type 1-infected women in labor and their newborns . No adverse effects of nevirapine were noted in any study mothers or infants . Following maternal dosing with 200 mg during labor , concentrations exceeding 100 ng/mL ( 10 times the in vitro IC50 ) were achieved in the newborns .  Nevirapine elimination was prolonged in both mothers and infants , with median half-lives ranging from 36.8 to 65.7 h. Administration of 200 mg orally to the mothers in labor and of a single 2-mg/kg oral dose to the infants at 48 - 72 h after birth maintained serum concentrations in the infants > 100 ng/mL through 7 days of life BACKGROUND An intensive , prospect i ve , 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 ) sample s 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 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 underst and the impact of maternal ARV treatment on breast-feeding HIV-1 transmission , infant toxicity , and HIV-1 resistance mutations among infected infants Objectives : Nucleoside analog reverse transcriptase inhibitors ( NRTI ) are used in virtually all anti-HIV regimens . Clinical response depends on the intracellular formation of the pharmacologically active triphosphate moiety . Our objective was to quantify the pharmacological characteristics of zidovudine and lamivudine triphosphate in HIV-infected individuals . Methods : Peripheral blood mononuclear cells were obtained at multiple planned intervals from antiretroviral-naive adults participating in a study of zidovudine , lamivudine and indinavir , and triphosphate levels were determined by immunoassay and high-performance liquid chromatography/mass spectrometry .  Plasma HIV-RNA , CD4 cell counts , and plasma drug concentrations were collected over 18 months . Data were analysed using non-parametric , regression and time-to-event methods . Results : Thirty-three subjects were evaluated . The estimated half-lives of  zidovudine  and lamivudine triphosphate were 7 and 22 h , respectively . Triphosphate concentrations were elevated in individuals with low baseline CD4 cell counts . Triphosphate concentrations in women were higher than in men by 2.3 and 1.6-fold for zidovudine and lamivudine , respectively . Women reached an HIV-RNA level under 50 copies/ml twice as fast as men . Zidovudine triphosphate above 30 fmol/106 cells was independently predictive of the time to under 50 copies/ml . Lamivudine triphosphate above 7017 fmol/106 cells was independently predictive of a longer virological response .  Indinavir concentrations were related to antiviral responses in univariate analyses . Conclusion : Zidovudine and lamivudine triphosphate concentration thresholds were independently associated with the antiviral activity of zidovudine , lamivudine , and indinavir . The significantly elevated triphosphate concentrations in women and individuals with low baseline CD4 cell counts , groups that historically experience high rates of serious NRTI toxicities , provide a hypothesis for the pathogenesis of these events Background : Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking . Methods : The HIV Prevention Trials Network 057 protocol was a phase 1 , open-label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate ( TDF ) in HIV-infected women during labor and their infants during the first week of life with 4 dosing cohorts :  maternal 600 mg doses/no infant dosing ; no maternal dosing/infant 4 mg/kg doses on days 0 , 3 , and 5 ; maternal 900 mg doses/infant 6 mg/kg doses on days 0 , 3 , and 5 ; maternal 600 mg doses/infant 6 mg/kg daily for 7 doses . Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants .  Plasma , amniotic fluid , and breast milk tenofovir concentrations were determined by liquid chromatographic – t and em mass spectrometric assay . The pharmacokinetic target was for infant tenofovir concentration throughout the first week of life to exceed 50 ng/mL , the median trough tenofovir concentration in adults receiving st and ard chronic TDF dosing . Results : One hundred twenty-two mother – infant pairs from Malawi and Brazil were studied .  Tenofovir exposure in mothers receiving 600 and 900 mg exceeded that in nonpregnant adults receiving st and ard 300 mg doses . Tenofovir elimination in the infants was equivalent to that in older children and adults , and trough tenofovir plasma concentrations exceeded 50 ng/mL in 74%–97 % of infants receiving daily dosing . Conclusions : A TDF dosing regimen of 600 mg during labor and daily infant doses of 6 mg/kg maintains infant tenofovir plasma concentration above 50 ng/mL throughout the first week of life and should be used in the studies of TDF efficacy for HIV prevention of mother-to-child transmission and early infant treatment Background : The optimal neonatal antiretroviral ( ARV ) regimen for prevention of HIV mother-to-child transmission ( MTCT ) is unknown for infants born to mothers who receive no ARVs during pregnancy . Methods : As part of a protocol comparing the efficacy of 3 neonatal ARV regimens in preventing HIV-1 MTCT in neonates born to mothers who receive no prenatal treatment with ARVs , we devised a 3-dose nevirapine ( NVP ) regimen with the goal of maintaining the NVP plasma concentration > 100 ng/mL ( 10 times the in vitro median inhibitory concentration of 10 ng/mL ) during the first 2 weeks of life .  NVP concentrations were measured in 14 newborns participating in a pharmacokinetics sub study during the second week of life and in single sample s from 30 more newborns on day 10 to 14 . Results : The median NVP elimination half-life was 30.2 hours ( range : 17.8 to 50.3 hours ) . The  NVP concentration remained greater than the target of 100 ng/mL in all sample s collected through day 10 of life . By day 14 , more than half of the newborns in the pharmacokinetic sub study had NVP levels < 100 ng/mL , although only 1 neonate had no detectable NVP . Conclusion : Although this regimen failed to meet our 100-ng/mL target , it did maintain detectable  NVP concentrations in nearly all newborns through the end of the second week of life and is to be used in the parent efficacy protocol Single-dose nevirapine for mothers and newborns at delivery is the simplest prevention strategy for vertical HIV-1 transmission and hence widely used in re source -constrained setting s. 
    Output:
    
Conclusions Transfer to untreated infants appears quantitatively important for some NRTIs and NNRTIs .