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Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children.

Abstract With limited and low-genetic barrier drugs used for the prevention of mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa, vertically transmitted HIV-1 drug-resistance (HIVDR) is concerning and might prompt optimal pediatric strategies.The aim of this study was to ascertain HIVDR and viral-tropism in majority and minority populations among Cameroonian vertically infected children.A comparative analysis among 18 HIV-infected children (7 from PMTCT-exposed mothers and 11 from mothers without PMTCT-exposure) was performed. HIVDR and HIV-1 co-receptor usage was evaluated by analyzing sequences obtained by both Sanger sequencing and ultra-deep 454-pyrosequencing (UDPS), set at 1% threshold.Overall, median (interquartile range) age, viremia, and CD4 count were 6 (4-10) years, 5.5 (4.9-6.0) log10 copies/mL, and 526 (282-645) cells/mm, respectively. All children had wild-type viruses through both Sanger sequencing and UDPS, except for 1 PMTCT-exposed infant harboring minority K103N (8.31%), born to a mother exposed to AZT+3TC+NVP. X4-tropic viruses were found in 5 of 15 (33.3%) children (including 2 cases detected only by UDPS). Rate of X4-tropic viruses was 0% (0/6) below 5 years (also as minority species), and became relatively high above 5 years (55.6% [5/9], P = .040. X4-tropic viruses were higher with CD4 ≤15% (4/9 [44.4%]) versus CD4 >15% (1/6 [16.7%], P = .580); similarly for CD4 ≤200 (3/4 [75%]) versus CD4 >200 (2/11 [18.2%] cells/mm, P = .077.NGS has the ability of excluding NRTI- and NNRTI-mutations as minority species in all but 1 children, thus supporting the safe use of these drug-classes in those without such mutations, henceforth sparing ritonavir-boosted protease inhibitors or integrase inhibitors for the few remaining cases. In children under five years, X4-tropic variants would be rare, suggesting vertical-transmission with CCR5-tropic viruses and possible maraviroc usage at younger ages.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title medicine
Publication Year Start




PMID- 29595649
OWN - NLM
STAT- MEDLINE
DCOM- 20180411
LR  - 20180411
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Linking)
VI  - 97
IP  - 13
DP  - 2018 Mar
TI  - Next-generation sequencing provides an added value in determining drug resistance
      and viral tropism in Cameroonian HIV-1 vertically infected children.
PG  - e0176
LID - 10.1097/MD.0000000000010176 [doi]
AB  - With limited and low-genetic barrier drugs used for the prevention of
      mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa, vertically
      transmitted HIV-1 drug-resistance (HIVDR) is concerning and might prompt optimal 
      pediatric strategies.The aim of this study was to ascertain HIVDR and
      viral-tropism in majority and minority populations among Cameroonian vertically
      infected children.A comparative analysis among 18 HIV-infected children (7 from
      PMTCT-exposed mothers and 11 from mothers without PMTCT-exposure) was performed. 
      HIVDR and HIV-1 co-receptor usage was evaluated by analyzing sequences obtained
      by both Sanger sequencing and ultra-deep 454-pyrosequencing (UDPS), set at 1%
      threshold.Overall, median (interquartile range) age, viremia, and CD4 count were 
      6 (4-10) years, 5.5 (4.9-6.0) log10 copies/mL, and 526 (282-645) cells/mm,
      respectively. All children had wild-type viruses through both Sanger sequencing
      and UDPS, except for 1 PMTCT-exposed infant harboring minority K103N (8.31%),
      born to a mother exposed to AZT+3TC+NVP. X4-tropic viruses were found in 5 of 15 
      (33.3%) children (including 2 cases detected only by UDPS). Rate of X4-tropic
      viruses was 0% (0/6) below 5 years (also as minority species), and became
      relatively high above 5 years (55.6% [5/9], P = .040. X4-tropic viruses were
      higher with CD4 </=15% (4/9 [44.4%]) versus CD4 >15% (1/6 [16.7%], P = .580);
      similarly for CD4 </=200 (3/4 [75%]) versus CD4 >200 (2/11 [18.2%] cells/mm, P = 
      .077.NGS has the ability of excluding NRTI- and NNRTI-mutations as minority
      species in all but 1 children, thus supporting the safe use of these drug-classes
      in those without such mutations, henceforth sparing ritonavir-boosted protease
      inhibitors or integrase inhibitors for the few remaining cases. In children under
      five years, X4-tropic variants would be rare, suggesting vertical-transmission
      with CCR5-tropic viruses and possible maraviroc usage at younger ages.
FAU - Fokam, Joseph
AU  - Fokam J
FAU - Bellocchi, Maria C
AU  - Bellocchi MC
AD  - University of Rome Tor Vergata, Rome, Italy.
FAU - Armenia, Daniele
AU  - Armenia D
AD  - University of Rome Tor Vergata, Rome, Italy.
FAU - Nanfack, Aubin J
AU  - Nanfack AJ
FAU - Carioti, Luca
AU  - Carioti L
AD  - University of Rome Tor Vergata, Rome, Italy.
FAU - Continenza, Fabio
AU  - Continenza F
AD  - National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome,
      Italy.
FAU - Takou, Desire
AU  - Takou D
AD  - Chantal Biya International Reference Centre for research on HIV/AIDS Prevention
      and Management, Yaounde, Cameroon.
FAU - Temgoua, Edith S
AU  - Temgoua ES
AD  - Chantal Biya International Reference Centre for research on HIV/AIDS Prevention
      and Management, Yaounde, Cameroon.
FAU - Tangimpundu, Charlotte
AU  - Tangimpundu C
AD  - Chantal Biya International Reference Centre for research on HIV/AIDS Prevention
      and Management, Yaounde, Cameroon.
FAU - Torimiro, Judith N
AU  - Torimiro JN
FAU - Koki, Paul N
AU  - Koki PN
FAU - Fokunang, Charles N
AU  - Fokunang CN
FAU - Cappelli, Giulia
AU  - Cappelli G
AD  - National Research Council.
FAU - Ndjolo, Alexis
AU  - Ndjolo A
FAU - Colizzi, Vittorio
AU  - Colizzi V
FAU - Ceccherini-Silberstein, Francesca
AU  - Ceccherini-Silberstein F
AD  - University of Rome Tor Vergata, Rome, Italy.
FAU - Perno, Carlo-Federico
AU  - Perno CF
FAU - Santoro, Maria M
AU  - Santoro MM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Anti-HIV Agents)
RN  - 0 (RNA, Viral)
SB  - AIM
SB  - IM
MH  - Anti-HIV Agents/administration & dosage/*therapeutic use
MH  - CD4 Lymphocyte Count
MH  - Cameroon
MH  - Child
MH  - Child, Preschool
MH  - Drug Resistance, Viral/*genetics
MH  - Female
MH  - HIV Infections/*transmission/virology
MH  - HIV-1/*genetics
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Infectious Disease Transmission, Vertical/*prevention & control
MH  - Male
MH  - RNA, Viral
MH  - Viral Tropism/genetics
EDAT- 2018/03/30 06:00
MHDA- 2018/04/12 06:00
CRDT- 2018/03/30 06:00
PHST- 2018/03/30 06:00 [entrez]
PHST- 2018/03/30 06:00 [pubmed]
PHST- 2018/04/12 06:00 [medline]
AID - 10.1097/MD.0000000000010176 [doi]
AID - 00005792-201803300-00022 [pii]
PST - ppublish
SO  - Medicine (Baltimore). 2018 Mar;97(13):e0176. doi: 10.1097/MD.0000000000010176.