The within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children

Abstract As the immune system develops with age, children combat infections better. HIV-1, however, targets an activated immune system, potentially rendering children increasingly permissive to HIV-1 infection as they grow. How HIV-1 fitness changes with age in children is unknown. Here, we estimate...

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Autores principales:	Pradeep Nagaraja, Bindu P. Gopalan, Reena R. D’Souza, Debolina Sarkar, Niharika Rajnala, Narendra M. Dixit, Anita Shet
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7b746e4219a4abbbee955fa77d3dd3b
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spelling	oai:doaj.org-article:c7b746e4219a4abbbee955fa77d3dd3b2021-12-02T14:06:55ZThe within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children10.1038/s41598-021-82293-22045-2322https://doaj.org/article/c7b746e4219a4abbbee955fa77d3dd3b2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82293-2https://doaj.org/toc/2045-2322Abstract As the immune system develops with age, children combat infections better. HIV-1, however, targets an activated immune system, potentially rendering children increasingly permissive to HIV-1 infection as they grow. How HIV-1 fitness changes with age in children is unknown. Here, we estimated the within-host basic reproductive ratio, R 0, a marker of viral fitness, in HIV-1 subtype C-infected children in India, aged between 84 days and 17 years. We measured serial viral load and CD4 T cell counts in 171 children who initiated first-line ART. For 25 children, regular and frequent measurements provided adequate data points for analysis using a mathematical model of viral dynamics to estimate R 0. For the rest, we used CD4 counts for approximate estimation of R 0. The viral load decline during therapy was biphasic. The mean lifespans of productively and long-lived infected cells were 1.4 and 27.8 days, respectively. The mean R 0 was 1.5 in children aged < 5 years, increased with age, and approached 6.0 at 18 years, close to 5.8 estimated previously for adults. The tolerogenic immune environment thus compromises HIV-1 fitness in young children. Early treatment initiation, when the R 0 is small, will likely improve viral control, in addition to suppressing the latent reservoir.Pradeep NagarajaBindu P. GopalanReena R. D’SouzaDebolina SarkarNiharika RajnalaNarendra M. DixitAnita ShetNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pradeep Nagaraja Bindu P. Gopalan Reena R. D’Souza Debolina Sarkar Niharika Rajnala Narendra M. Dixit Anita Shet The within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children
description	Abstract As the immune system develops with age, children combat infections better. HIV-1, however, targets an activated immune system, potentially rendering children increasingly permissive to HIV-1 infection as they grow. How HIV-1 fitness changes with age in children is unknown. Here, we estimated the within-host basic reproductive ratio, R 0, a marker of viral fitness, in HIV-1 subtype C-infected children in India, aged between 84 days and 17 years. We measured serial viral load and CD4 T cell counts in 171 children who initiated first-line ART. For 25 children, regular and frequent measurements provided adequate data points for analysis using a mathematical model of viral dynamics to estimate R 0. For the rest, we used CD4 counts for approximate estimation of R 0. The viral load decline during therapy was biphasic. The mean lifespans of productively and long-lived infected cells were 1.4 and 27.8 days, respectively. The mean R 0 was 1.5 in children aged < 5 years, increased with age, and approached 6.0 at 18 years, close to 5.8 estimated previously for adults. The tolerogenic immune environment thus compromises HIV-1 fitness in young children. Early treatment initiation, when the R 0 is small, will likely improve viral control, in addition to suppressing the latent reservoir.
format	article
author	Pradeep Nagaraja Bindu P. Gopalan Reena R. D’Souza Debolina Sarkar Niharika Rajnala Narendra M. Dixit Anita Shet
author_facet	Pradeep Nagaraja Bindu P. Gopalan Reena R. D’Souza Debolina Sarkar Niharika Rajnala Narendra M. Dixit Anita Shet
author_sort	Pradeep Nagaraja
title	The within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children
title_short	The within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children
title_full	The within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children
title_fullStr	The within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children
title_full_unstemmed	The within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children
title_sort	within-host fitness of hiv-1 increases with age in art-naïve hiv-1 subtype c infected children
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c7b746e4219a4abbbee955fa77d3dd3b
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The within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children

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