Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children. Issue 13 (March 2018)

• Record Type: Journal Article
• Authors: Fokam, Joseph; Bellocchi, Maria C.; Armenia, Daniele; Nanfack, Aubin J.; Carioti, Luca; Continenza, Fabio; Takou, Desire; Temgoua, Edith S.; Tangimpundu, Charlotte; Torimiro, Judith N.; Koki, Paul N.; Fokunang, Charles N.; Cappelli, Giulia; Ndjolo, Alexis; Colizzi, Vittorio; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Santoro, Maria M.
• Other Names: Wang. Leyi section editor.
• Is Part Of: Medicine. Volume 97:Issue 13(2018)
• Publication Date: 2018-03
• Subjects: children -- coreceptor usage -- HIV-1 drug resistance -- next-generation sequencing -- PMTCT -- sanger sequencing; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000010176
• Languages: English
• ISSNs: 0025-7974

Abstract

Abstract : 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 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.