TY - JOUR
T1 - Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children.
AU - Fokam, Joseph
AU - Bellocchi, Maria C.
AU - Armenia, Daniele
AU - Nanfack, Aubin J.
AU - Carioti, Luca
AU - Continenza, Fabio
AU - Takou, Desire
AU - Temgoua, Edith S.
AU - Tangimpundu, Charlotte
AU - Torimiro, Judith N.
AU - Koki, Paul N.
AU - Fokunang, Charles N.
AU - Cappelli, Giulia
AU - Ndjolo, Alexis
AU - Colizzi, Vittorio
AU - Ceccherini-Silberstein, Francesca
AU - Perno, Carlo-Federico
AU - Santoro, Maria M.
N1 - PT: J; TC: 0; UT: MEDLINE:29595649
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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) log 10 copies/mL, and 526 (282-645) cells/mm 3, 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 3, 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.
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) log 10 copies/mL, and 526 (282-645) cells/mm 3, 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 3, 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.
U2 - 10.1097/MD.0000000000010176
DO - 10.1097/MD.0000000000010176
M3 - Article
SN - 0025-7974
VL - 97
SP - e0176-e0176
JO - Medicine (United States)
JF - Medicine (United States)
IS - 13
ER -