Adherence-Related Mechanisms of Breastmilk HIV-1 Transmission Public Deposited

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  • March 19, 2019
Creator
  • Davis, Nicole Lane
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Postpartum HIV transmission through breastfeeding accounts for up to 44% of infant HIV infections. Antiretroviral (ARV) drugs are administered to either the HIV-infected mother or HIV-exposed infant throughout breastfeeding to reduce HIV transmission risk. Suboptimal adherence to prescribed ARV regimens may partly explain breastmilk HIV transmission despite ARV use. The purpose of this dissertation was to 1) estimate adherence to postpartum ARVs, 2) quantify the effect of postpartum adherence on breastmilk HIV transmission, and 3) evaluate breastmilk HIV RNA concentration as a mediating factor between ARV adherence and breastmilk HIV transmission. We included mother-infant pairs randomized to receive 28 weeks of either triple maternal ARV or daily infant nevirapine as part of the Breastfeeding, Antiretrovirals, and Nutrition study. Among these, a cohort of 1479 mother-infant pairs was used to estimate the association between postpartum ARV adherence and breastmilk HIV-1 transmission between 5-38 weeks of age. Additionally, a case-cohort study including 263 mother-infant pairs was used to assess breastmilk viral load as a mediating factor between postpartum adherence and breastmilk HIV transmission. Adherence was measured over four time intervals using pill count, suspension bottle weight, and maternal self-report. RNA concentration was measured in both plasma and breastmilk at 5 time points. Infant HIV-1 infection was determined by DNA PCR every 2-6 weeks. Using pill count and bottle weight information, having > 90% adherence was associated with a 52% (95% CI 3-76%) relative reduction in the adjusted rate of breastmilk HIV-1 transmission by 38 weeks of age, compared with having <90% adherence. Having partial adherence (81-98%) was associated with a 77% (95% CI 33-92%) relative reduction in the adjusted odds of having detectable (> 40 copies/ml) breastmilk HIV RNA, compared with having poor adherence (0-80%). Detectable breastmilk HIV RNA was associated with 4.5 (95% CI 2.0-9.9) times the adjusted relative rate of BMK HIV-1 transmission by 28 weeks of infant's age, compared to having undetectable (<40 copies/ml) breastmilk HIV RNA. Maternal ARV adherence is associated with reduced breastmilk HIV transmission, at least partly mediated by reduced breastmilk HIV RNA. Effective adherence interventions may help to further prevent breastmilk HIV transmission.
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  • In Copyright
Advisor
  • Miller, William
Degree
  • Doctor of Philosophy
Graduation year
  • 2014
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