Maternal Human Immunodeficiency Virus (HIV) Drug Resistance Is Associated With Vertical Transmission and Is Prevalent in Infected Infants

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Abstract
We aimed to assess if maternal human immunodeficiency virus (HIV) drug resistance is associated with an increased risk of HIV vertical transmission and to describe the dynamics of drug resistance in HIV-infected infants. This was a case-control study of PROMISE study participants. “Cases” were mother-infant pairs with HIV vertical transmission during pregnancy or breastfeeding and “controls” were mother-infant pairs without transmission matched 1:3 by delivery date and clinical site. Genotypic HIV drug resistance analyses were performed on mothers’ and their infants’ plasma at or near the time of infant HIV diagnosis. Longitudinal analysis of genotypic resistance was assessed in available specimens from infants, from diagnosis and beyond, including antiretroviral therapy (ART) initiation and last study visits. Our analyses included 85 cases and 255 matched controls. Maternal HIV drug resistance, adjusted for plasma HIV RNA load at infant HIV diagnosis, enrollment CD4 count, and antepartum regimens, was not associated with in utero/peripartum HIV transmission. In contrast, both maternal plasma HIV RNA load and HIV drug resistance were independent risk factors associated with vertical transmission during breastfeeding. Furthermore, HIV drug resistance was selected across infected infants during infancy. Maternal HIV drug resistance and maternal viral load were independent risk factors for vertical transmission during breastfeeding, suggesting that nevirapine alone may be insufficient infant prophylaxis against drug-resistant variants in maternal breast milk. These findings support efforts to achieve suppression of HIV replication during pregnancy and suggest that breastfeeding infants may benefit from prophylaxis with a greater barrier to drug resistance than nevirapine alone.
Funding Information
  • National Institute of Allergy and Infectious Diseases
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • National Institute of Mental Health
  • National Institutes of Health (UM1AI068632, UM1AI068616, UM1AI106716)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275201800001I)
  • Molecular Profiling and Computational Biology Core of the University of Washington Fred Hutch Center for AIDS Research (P30 AI027757, HHSN275201300003C, T32 AI007509)

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