Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali

Josephine Brice, Mariam Sylla, Nathalie Desire, Sophie Sayon, Fatoumata Telly, Djeneba Bocar-Fofana, Robert Murphy, Gilles Peytavin, Souleymane Diallo, Eleni Nastouli, Vincent Calvez, Anne Geneviève Marcelin, Almoustapha Issiaka Maiga, Sidonie Lambert-Niclot

Research output: Contribution to journalArticle

Abstract

BACKGROUND: In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir. OBJECTIVES: To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA. METHODS: In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤50 copies/mL for at least 6 months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots. RESULTS: Children had a median age of 9.9 years at the time of inclusion (IQR = 7.6-13.4) and 3.3 years (IQR = 2-7) at ART initiation; median ART duration was 5.5 years (IQR = 3.7-7.3). The median level of total HIV DNA was 470 copies/106 cells with one patient presenting undetectable HIV DNA (<66 copies/106 cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI. CONCLUSIONS: While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir.

Original languageEnglish (US)
Pages (from-to)1272-1279
Number of pages8
JournalThe Journal of antimicrobial chemotherapy
Volume75
Issue number5
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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    Brice, J., Sylla, M., Desire, N., Sayon, S., Telly, F., Bocar-Fofana, D., Murphy, R., Peytavin, G., Diallo, S., Nastouli, E., Calvez, V., Marcelin, A. G., Issiaka Maiga, A., & Lambert-Niclot, S. (2020). Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali. The Journal of antimicrobial chemotherapy, 75(5), 1272-1279. https://doi.org/10.1093/jac/dkaa002