HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis.
Clement Zeh,Paul J. Weidle,Lillian Nafisa,Humphrey M. Lwamba,Jully A. Okonji,Emily Anyango,Philip Bondo,Rose Masaba,Mary Glenn Fowler,John N. Nkengasong,Michael C. Thigpen,Timothy K. Thomas +11 more
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Analysis of a substudy of the Kisumu breastfeeding trial reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs.Abstract:
Background: Nevirapine and lamivudine given to mothers are transmitted to infants via breastfeeding in quantities sufficient to have biologic effects on the virus; this may lead to an increased risk of a breastfed infant’s development of resistance to maternal antiretrovirals. The Kisumu Breastfeeding Study (KiBS), a single-arm open-label prevention of motherto-child HIV transmission (PMTCT) trial, assessed the safety and efficacy of zidovudine, lamivudine, and either nevirapine or nelfinavir given to HIV-infected women from 34 wk gestation through 6 mo of breastfeeding. Here, we present findings from a KiBS trial secondary analysis that evaluated the emergence of maternal ARV-associated resistance among 32 HIVinfected breastfed infants. Methods and Findings: All infants in the cohort were tested for HIV infection using DNA PCR at multiple study visits during the 24 mo of the study, and plasma RNA viral load for all HIV-PCR–positive infants was evaluated retrospectively. Specimens from mothers and infants with viral load .1,000 copies/ml were tested for HIV drug resistance mutations. Overall, 32 infants were HIV infected by 24 mo of age, and of this group, 24 (75%) infants were HIV infected by 6 mo of age. Of the 24 infants infected by 6 mo, nine were born to mothers on a nelfinavir-based regimen, whereas the remaining 15 were born to mothers on a nevirapine-based regimen. All infants were also given single-dose nevirapine within 48 hours of birth. We detected genotypic resistance mutations in none of eight infants who were HIV-PCR positive by 2 wk of age (specimens from six infants were not amplifiable), for 30% (6/20) at 6 wk, 63% (14/22) positive at 14 wk, and 67% (16/24) at 6 mo post partum. Among the 16 infants with resistance mutations by 6 mo post partum, the common mutations were M184V and K103N, conferring resistance to lamivudine and nevirapine, respectively. Genotypic resistance was detected among 9/9 (100%) and 7/15 (47%) infected infants whose mothers were on nelfinavir and nevirapine, respectively. No mutations were detected among the eight infants infected after the breastfeeding period (age 6 mo). Conclusions: Emergence of HIV drug resistance mutations in HIV-infected infants occurred between 2 wk and 6 mo post partum, most likely because of exposure to maternal ARV drugs through breast milk. Our findings may impact the choice of regimen for ARV treatment of HIV-infected breastfeeding mothers and their infected infants. Trial Registration: ClinicalTrials.gov NCT00146380 Please see later in the article for the Editors’ Summary.read more
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Adherence to antiretroviral therapy during and after pregnancy in low-income, middle-income, and high-income countries: a systematic review and meta-analysis.
Jean B. Nachega,Olalekan A. Uthman,Olalekan A. Uthman,Jean Anderson,Karl Peltzer,Karl Peltzer,Sarah Wampold,Mark F. Cotton,Edward J Mills,Yuh-Shan Ho,Jeffrey S. A. Stringer,Jeffrey S. A. Stringer,James McIntyre,Lynne M. Mofenson +13 more
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TL;DR: Both enzymatic and virologic data indicate that naturally occurring polymorphisms among different HIV subtypes can influence HIV-1 susceptibility to individual antiretroviral drugs and the propensity of HIV to acquire certain resistance mutations.
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Triple-Antiretroviral Prophylaxis to Prevent Mother-To- Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial
Timothy K. Thomas,Timothy K. Thomas,Rose Masaba,Craig B. Borkowf,Richard Ndivo,Clement Zeh,Clement Zeh,Ambrose O. Misore,Juliana A. Otieno,Denise J. Jamieson,Michael C. Thigpen,Marc Bulterys,Laurence Slutsker,Kevin M. De Cock,Kevin M. De Cock,Pauli N. Amornkul,Pauli N. Amornkul,Alan E. Greenberg,Mary Glenn Fowler +18 more
TL;DR: The Kisumu breastfeeding study (Kenya) was a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy.
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TL;DR: This review provides a detailed analysis of risks and benefits of B+.
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Early Antiretroviral Therapy and Mortality among HIV-Infected Infants
Avy Violari,Mark F. Cotton,Diana M. Gibb,Abdel Babiker,Jan Steyn,Shabir A. Madhi,Patrick Jean-Philippe,James McIntyre +7 more
TL;DR: Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%.
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Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice.
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TL;DR: Current knowledge of mother-to-child HIV transmission in developing countries is reviewed, key findings from the trials are summarized, future research requirements are outlined, and public health challenges of implementing perinatal HIV prevention interventions in resource-poor settings are described.
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