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

Overview

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.

authors

  • Permar, Sallie
  • Salazar, Maria G
  • Gao, Feng
  • Cai, Fangping
  • Learn, Gerald H
  • Kalilani, Linda
  • Hahn, Beatrice H
  • Shaw, George M
  • Salazar-Gonzalez, Jesus F

publication date

  • August 14, 2013

Research

keywords

  • Anti-HIV Agents
  • Drug Resistance, Viral
  • HIV Infections
  • HIV-1
  • Milk, Human
  • Nevirapine

Identity

PubMed Central ID

  • PMC3765243

Scopus Document Identifier

  • 84883033139

Digital Object Identifier (DOI)

  • 10.1186/1742-4690-10-88

PubMed ID

  • 23941304

Additional Document Info

volume

  • 10