Abstract:
:Single-dose nevirapine (sd-NVP) and extended NVP prophylaxis are widely used in resource-constrained settings to prevent vertical HIV-1 transmission. We assessed the pharmacokinetics of sd-NVP in 62 HIV-1-positive pregnant Ugandan woman and their newborns who were receiving sd-NVP prophylaxis to prevent mother-to-child HIV-1 transmission. Based on these data, we developed a mathematical model system to quantify the impact of different sd-NVP regimens at delivery and of extended infant NVP prophylaxis (6, 14, 21, 26, 52, 78, and 102 weeks) on the 2-year risk of HIV-1 transmission and development of drug resistance in mothers and their breast-fed infants. Pharmacokinetic parameter estimates and model-predicted HIV-1 transmission rates were very consistent with other studies. Predicted 2-year HIV-1 transmission risks were 35.8% without prophylaxis, 31.6% for newborn sd-NVP, 19.1% for maternal sd-NVP, and 19.7% for maternal/newborn sd-NVP. Maternal sd-NVP reduced newborn infection predominately by transplacental exchange, providing protective NVP concentrations to the newborn at delivery, rather than by maternal viral load reduction. Drug resistance was frequently selected in HIV-1-positive mothers after maternal sd-NVP. Extended newborn NVP prophylaxis further decreased HIV-1 transmission risks, but an overall decline in cost-effectiveness for increasing durations of newborn prophylaxis was indicated. The total number of infections with resistant virus in newborns was not increased by extended newborn NVP prophylaxis. The developed mathematical modeling framework successfully predicted the risk of HIV-1 transmission and resistance development and can be adapted to other drugs/drug combinations to a priori assess their potential in reducing vertical HIV-1 transmission and resistance spread.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Frank M,von Kleist M,Kunz A,Harms G,Schütte C,Kloft Cdoi
10.1128/AAC.00741-11subject
Has Abstractpub_date
2011-12-01 00:00:00pages
5529-40issue
12eissn
0066-4804issn
1098-6596pii
AAC.00741-11journal_volume
55pub_type
杂志文章abstract::The linkage between the macrolide efflux gene mef(I) and the chloramphenicol inactivation gene catQ was first described in Streptococcus pneumoniae (strain Spn529), where the two genes are located in a module designated IQ element. Subsequently, two different defective IQ elements were detected in Streptococcus pyogen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03638-14
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2002-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.1.120
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02242-18
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.49.10.4137-4143.2005
更新日期:2005-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.7.1670
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01006-18
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.10.3236-3242.2002
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02234-15
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.9.3001-3012.2002
更新日期:2002-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.7.1767
更新日期:1999-07-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.2.224
更新日期:1985-02-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02320-13
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.3.421
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.11.2484
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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更新日期:2002-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.1.130
更新日期:1980-07-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.7.2144-2146.2001
更新日期:2001-07-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2003-07-01 00:00:00