Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis

Retrovirology. 2013 Aug 14:10:88. doi: 10.1186/1742-4690-10-88.

Abstract

Background: Intrapartum administration of single-dose nevirapine (sdNVP) reduces perinatal HIV-1 transmission in resource-limiting settings by half. Yet this strategy has limited effect on subsequent breast milk transmission, making the case for new treatment approaches to extend maternal/infant antiretroviral prophylaxis through the period of lactation. Maternal and transmitted infant HIV-1 variants frequently develop NVP resistance mutations following sdNVP, complicating subsequent treatment/prophylaxis regimens. However, it is not clear whether NVP-resistant viruses are transmitted via breastfeeding or arise de novo in the infant.

Findings: We performed a detailed HIV genetic analysis using single genome sequencing to identify the origin of drug-resistant variants in an sdNVP-treated postnatally-transmitting mother-infant pair. Phylogenetic analysis of HIV sequences from the child revealed low-diversity variants indicating infection by a subtype C single transmitted/founder virus that shared full-length sequence identity with a clonally-amplified maternal breast milk virus variant harboring the K103N NVP resistance mutation.

Conclusion: In this mother/child pair, clonal amplification of maternal NVP-resistant HIV variants present in systemic and mammary gland compartments following intrapartum sdNVP represents one source of transmitted NVP-resistant variants that is responsible for the acquisition of drug resistant virus by the breastfeeding infant. This finding emphasizes the need for combination antiretroviral prophylaxis to prevent mother-to-child HIV transmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacology
  • Chemoprevention / methods
  • Cluster Analysis
  • Drug Resistance, Viral*
  • Female
  • Genotype
  • HIV Infections / prevention & control*
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Humans
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control
  • Milk, Human / virology*
  • Molecular Epidemiology
  • Molecular Sequence Data
  • Nevirapine / administration & dosage*
  • Nevirapine / pharmacology
  • Phylogeny
  • Pregnancy
  • RNA, Viral / genetics
  • Sequence Analysis, DNA
  • Sequence Homology

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • Nevirapine

Associated data

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