TY - JOUR
T1 - Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali
AU - Brice, Josephine
AU - Sylla, Mariam
AU - Desire, Nathalie
AU - Sayon, Sophie
AU - Telly, Fatoumata
AU - Bocar-Fofana, Djeneba
AU - Murphy, Robert
AU - Peytavin, Gilles
AU - Diallo, Souleymane
AU - Nastouli, Eleni
AU - Calvez, Vincent
AU - Marcelin, Anne Geneviève
AU - Issiaka Maiga, Almoustapha
AU - Lambert-Niclot, Sidonie
N1 - Funding Information:
This work was supported by the Agence Nationale de la Recherche sur le SIDA (ANRS) and Early-treated Perinatally HIV-infected Individual: Improving Children's Actual Life with Novel Immunotherapeutic Strategies (EPIICAL). The EPIICAL project is funded through an independent grant by ViiV HealthcareUK.
Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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. 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.
AB - 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. 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.
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U2 - 10.1093/jac/dkaa002
DO - 10.1093/jac/dkaa002
M3 - Article
C2 - 32073629
AN - SCOPUS:85084024878
VL - 75
SP - 1272
EP - 1279
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 5
ER -
