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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Bibliographic Details
Published in:Journal of applied mathematics 2021, Vol.2021, p.1-15
Main Authors: Nampala, Hasifa, Jablonska-Sabuka, Matylda, Singull, Martin
Format: Article
Language:English
Subjects:
Antigens
Control theory
Cytotoxicity
DNA methylation
Drug therapy
Hepatitis B
HIV
Human immunodeficiency virus
Infections
Kinases
Liver
Lymphocytes
Mathematical analysis
Mathematical models
Mortality
Optimal control
Partial differential equations
Patients
Viral infections
Viruses
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Summary: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.
ISSN:1110-757X
1687-0042
1687-0042
DOI:10.1155/2021/5525857