Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children

Djeneba B. Fofana; Houdou Diarra; Ibrahima Guindo; Mahamadou K. Savadogo; Marceline d’Almeida; Fatoumata I. Diallo; Aliou Baldé; Cathia Soulié; Amadou Kone; Anne Geneviève Marcelin; Almoustapha I. Maiga; Sidonie Lambert-Niclot; Mamoudou Maiga; Sally McFall; Claudia A. Hawkins; Robert L. Murphy; Mariam Sylla; Christine Katlama; Jane L. Holl; Vincent Calvez; Laurence Morand-Joubert

doi:10.3390/v15020546

Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children

Djeneba B. Fofana^*, Houdou Diarra, Ibrahima Guindo, Mahamadou K. Savadogo, Marceline d’Almeida, Fatoumata I. Diallo, Aliou Baldé, Cathia Soulié, Amadou Kone, Anne Geneviève Marcelin, Almoustapha I. Maiga, Sidonie Lambert-Niclot, Mamoudou Maiga, Sally McFall, Claudia A. Hawkins, Robert L. Murphy, Mariam Sylla, Christine Katlama, Jane L. Holl, Vincent CalvezLaurence Morand-Joubert

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

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.

Original language	English (US)
Article number	546
Journal	Viruses
Volume	15
Issue number	2
DOIs	https://doi.org/10.3390/v15020546
State	Published - Feb 2023

Funding

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. 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.

Keywords

Africa
HIV-1
children
integrase
polymorphism
resistance

ASJC Scopus subject areas

Infectious Diseases
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/v15020546

Cite this

Fofana, D. B., Diarra, H., Guindo, I., Savadogo, M. K., d’Almeida, M., Diallo, F. I., Baldé, A., Soulié, C., Kone, A., Marcelin, A. G., Maiga, A. I., Lambert-Niclot, S., Maiga, M., McFall, S., Hawkins, C. A., Murphy, R. L., Sylla, M., Katlama, C., Holl, J. L., ... Morand-Joubert, L. (2023). Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children. Viruses, 15(2), Article 546. https://doi.org/10.3390/v15020546

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title = "Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children",

abstract = "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 na{\"i}ve to INI treatment, 56 were na{\"i}ve 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-na{\"i}ve 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-na{\"i}ve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa.",

keywords = "Africa, HIV-1, children, integrase, polymorphism, resistance",

author = "Fofana, {Djeneba B.} and Houdou Diarra and Ibrahima Guindo and Savadogo, {Mahamadou K.} and Marceline d{\textquoteright}Almeida and Diallo, {Fatoumata I.} and Aliou Bald{\'e} and Cathia Souli{\'e} and Amadou Kone and Marcelin, {Anne Genevi{\`e}ve} and Maiga, {Almoustapha I.} and Sidonie Lambert-Niclot and Mamoudou Maiga and Sally McFall and Hawkins, {Claudia A.} and Murphy, {Robert L.} and Mariam Sylla and Christine Katlama and Holl, {Jane L.} and Vincent Calvez and Laurence Morand-Joubert",

note = "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{\textquoteright}s Institute for Global Health Catalyzer program, the National Institutes of Health, and the HBNU Consortium. Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = feb,

doi = "10.3390/v15020546",

language = "English (US)",

volume = "15",

journal = "Viruses",

issn = "1999-4915",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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Fofana, DB, Diarra, H, Guindo, I, Savadogo, MK, d’Almeida, M, Diallo, FI, Baldé, A, Soulié, C, Kone, A, Marcelin, AG, Maiga, AI, Lambert-Niclot, S, Maiga, M , McFall, S , Hawkins, CA , Murphy, RL, Sylla, M, Katlama, C, Holl, JL, Calvez, V & Morand-Joubert, L 2023, 'Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children', Viruses, vol. 15, no. 2, 546. https://doi.org/10.3390/v15020546

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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JO - Viruses

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ER -

Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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