Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes

The biggest challenge of treating HIV is rampant liver-related morbidity and mortality. This is, to some extent, attributed to hepatocytes acting as viral reservoirs to both HIV and HBV. Viral reservoirs harbour latent provirus, rendering it inaccessible by combinational antiretroviral therapy (cART...

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Autores principales:	Hasifa Nampala, Matylda Jablonska-Sabuka, Martin Singull
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Mathematics QA1-939
Acceso en línea:	https://doaj.org/article/a0b00266979c4b64b0e039ba9997e2de
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spelling	oai:doaj.org-article:a0b00266979c4b64b0e039ba9997e2de2021-11-29T00:56:51ZMathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes1687-004210.1155/2021/5525857https://doaj.org/article/a0b00266979c4b64b0e039ba9997e2de2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/5525857https://doaj.org/toc/1687-0042The biggest challenge of treating HIV is rampant liver-related morbidity and mortality. This is, to some extent, attributed to hepatocytes acting as viral reservoirs to both HIV and HBV. Viral reservoirs harbour latent provirus, rendering it inaccessible by combinational antiretroviral therapy (cART) that is specific to actively proliferating virus. Latency reversal agents (LRA) such as Shock and kill or lock and block, aiming at activating the latently infected cells, have been developed. However, they are CD4+ cell-specific only. There is evidence that the low replication level of HIV in hepatocytes is mainly due to the latency of the provirus in these cells. LRA are developed to reduce the number of latently infected cells; however, the impact of the period viral latency in hepatocytes especially, during HIV/HBV coinfection, needs to be investigated. Viral coinfection coupled with lifelong treatment of HIV/HBV necessitates investigation for the optimal control strategy. We propose a coinfection mathematical model with delay and use optimal control theory to analyse the effect of viral latency in hepatocytes on the dynamics of HIV/HBV coinfection. Analytical results indicate that HBV cannot take a competitive exclusion against HIV; thus, the coinfection endemic equilibrium implies chronic HBV in HIV-infected patients. Numerical and analytical results indicate that both HIV and HBV viral loads are higher with longer viral latency period in hepatocytes, which indicates the need to upgrade LRA to other non-CD4+ cell viral reservoirs. Higher viral load caused by viral latency coupled with the effects of cART partly explains why liver-related complications are the leading cause of mortality in HIV-infected persons.Hasifa NampalaMatylda Jablonska-SabukaMartin SingullHindawi LimitedarticleMathematicsQA1-939ENJournal of Applied Mathematics, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mathematics QA1-939
spellingShingle	Mathematics QA1-939 Hasifa Nampala Matylda Jablonska-Sabuka Martin Singull Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes
description	The biggest challenge of treating HIV is rampant liver-related morbidity and mortality. This is, to some extent, attributed to hepatocytes acting as viral reservoirs to both HIV and HBV. Viral reservoirs harbour latent provirus, rendering it inaccessible by combinational antiretroviral therapy (cART) that is specific to actively proliferating virus. Latency reversal agents (LRA) such as Shock and kill or lock and block, aiming at activating the latently infected cells, have been developed. However, they are CD4+ cell-specific only. There is evidence that the low replication level of HIV in hepatocytes is mainly due to the latency of the provirus in these cells. LRA are developed to reduce the number of latently infected cells; however, the impact of the period viral latency in hepatocytes especially, during HIV/HBV coinfection, needs to be investigated. Viral coinfection coupled with lifelong treatment of HIV/HBV necessitates investigation for the optimal control strategy. We propose a coinfection mathematical model with delay and use optimal control theory to analyse the effect of viral latency in hepatocytes on the dynamics of HIV/HBV coinfection. Analytical results indicate that HBV cannot take a competitive exclusion against HIV; thus, the coinfection endemic equilibrium implies chronic HBV in HIV-infected patients. Numerical and analytical results indicate that both HIV and HBV viral loads are higher with longer viral latency period in hepatocytes, which indicates the need to upgrade LRA to other non-CD4+ cell viral reservoirs. Higher viral load caused by viral latency coupled with the effects of cART partly explains why liver-related complications are the leading cause of mortality in HIV-infected persons.
format	article
author	Hasifa Nampala Matylda Jablonska-Sabuka Martin Singull
author_facet	Hasifa Nampala Matylda Jablonska-Sabuka Martin Singull
author_sort	Hasifa Nampala
title	Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes
title_short	Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes
title_full	Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes
title_fullStr	Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes
title_full_unstemmed	Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes
title_sort	mathematical analysis of the role of hiv/hbv latency in hepatocytes
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/a0b00266979c4b64b0e039ba9997e2de
work_keys_str_mv	AT hasifanampala mathematicalanalysisoftheroleofhivhbvlatencyinhepatocytes AT matyldajablonskasabuka mathematicalanalysisoftheroleofhivhbvlatencyinhepatocytes AT martinsingull mathematicalanalysisoftheroleofhivhbvlatencyinhepatocytes
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Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes

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