TY - JOUR
T1 - Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children
AU - Fofana, Djeneba B.
AU - Diarra, Houdou
AU - Guindo, Ibrahima
AU - Savadogo, Mahamadou K.
AU - d’Almeida, Marceline
AU - Diallo, Fatoumata I.
AU - Baldé, Aliou
AU - Soulié, Cathia
AU - Kone, Amadou
AU - Marcelin, Anne Geneviève
AU - Maiga, Almoustapha I.
AU - Lambert-Niclot, Sidonie
AU - Maiga, Mamoudou
AU - McFall, Sally
AU - Hawkins, Claudia A.
AU - Murphy, Robert L.
AU - Sylla, Mariam
AU - Katlama, Christine
AU - Holl, Jane L.
AU - Calvez, Vincent
AU - Morand-Joubert, Laurence
N1 - Funding Information:
This specific research received no external funding. D.B.F. is independently supported by Fogarty International Center and the Office of the Director of the National Institutes of Health, Career Development Award K43TW011957 and the Agence Nationale de la Recherche sur le SIDA et les Maladies Infectieuses Emergentes (ANRS MIE) ANRS-MIE22295.
Funding Information:
We would like to acknowledge the Agence Nationale de la Recherche sur le SIDA et les Maladies Infectieuses Emergentes (ANRS MIE) for her support through the Laboratory of virology Saint-Antoine Hospital in Paris and the “Building the Next Generation of Researchers in TB/HIV Diagnostics in Mali (B-NextGen) Mali”, under award number D43TW010350. The authors are also grateful to the Northwestern University’s Institute for Global Health Catalyzer program, the National Institutes of Health, and the HBNU Consortium.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/2
Y1 - 2023/2
N2 - Integrase inhibitors (INIs) are a potent option for HIV treatment. Limited data exist on INI resistance in West Africa, particularly in children living with HIV/AIDS. We determined the prevalence of integrase gene polymorphisms and the frequency of naturally occurring amino acid (aa) substitutions at positions associated with INI resistance. Dried blood spot (DBS) samples were obtained from one hundred and seven (107) HIV-1-infected children aged less than 15 years old in two West African countries, Benin and Mali. All children were naïve to INI treatment, 56 were naïve to anti-retroviral therapy (ART), and 51 had received ART. Genetic sequencing of HIV integrase was successful in 75 samples. The aa changes at integrase positions associated with INI resistance were examined according to the Stanford HIV Genotypic Resistance database. The median ages were 2.6 and 10 years for ART-naïve and -treated children, respectively. The most common subtypes observed were CRF02_AG (74.7%) followed by CRF06_cpx (20%). No major INI-resistance mutations at positions 66, 92, 121, 143, 147, 148, 155, and 263 were detected. The most prevalent INI accessory resistance mutations were: L74I/M (14/75, 18.6%) followed by E157Q (8/75, 10.6%), G163E/N/T/Q (5/75, 6.6%), Q95A/H/P (2/75, 2.6%), and T97A (4/75, 5.3%). Other substitutions observed were M50I/L/P, H51E/P/S/Q, I72V, T112V, V201I, and T206S. Polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI-resistance pathways were detected. However, no transmitted drug resistance (TDR) to INI was detected among samples of INI-naïve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa.
AB - Integrase inhibitors (INIs) are a potent option for HIV treatment. Limited data exist on INI resistance in West Africa, particularly in children living with HIV/AIDS. We determined the prevalence of integrase gene polymorphisms and the frequency of naturally occurring amino acid (aa) substitutions at positions associated with INI resistance. Dried blood spot (DBS) samples were obtained from one hundred and seven (107) HIV-1-infected children aged less than 15 years old in two West African countries, Benin and Mali. All children were naïve to INI treatment, 56 were naïve to anti-retroviral therapy (ART), and 51 had received ART. Genetic sequencing of HIV integrase was successful in 75 samples. The aa changes at integrase positions associated with INI resistance were examined according to the Stanford HIV Genotypic Resistance database. The median ages were 2.6 and 10 years for ART-naïve and -treated children, respectively. The most common subtypes observed were CRF02_AG (74.7%) followed by CRF06_cpx (20%). No major INI-resistance mutations at positions 66, 92, 121, 143, 147, 148, 155, and 263 were detected. The most prevalent INI accessory resistance mutations were: L74I/M (14/75, 18.6%) followed by E157Q (8/75, 10.6%), G163E/N/T/Q (5/75, 6.6%), Q95A/H/P (2/75, 2.6%), and T97A (4/75, 5.3%). Other substitutions observed were M50I/L/P, H51E/P/S/Q, I72V, T112V, V201I, and T206S. Polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI-resistance pathways were detected. However, no transmitted drug resistance (TDR) to INI was detected among samples of INI-naïve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa.
KW - Africa
KW - HIV-1
KW - children
KW - integrase
KW - polymorphism
KW - resistance
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UR - http://www.scopus.com/inward/citedby.url?scp=85148973074&partnerID=8YFLogxK
U2 - 10.3390/v15020546
DO - 10.3390/v15020546
M3 - Article
C2 - 36851760
AN - SCOPUS:85148973074
SN - 1999-4915
VL - 15
JO - Viruses
JF - Viruses
IS - 2
M1 - 546
ER -
