Modelling hepatotoxicity and antiretroviral therapeutic effect in HIV/HBV coinfection

Nampala, Hasifa; Luboobi, Livingstone S.; Mugisha, Johnny; Obua, Celestino; Jabłońska-Sabuka, Matylda

doi:10.1016/j.mbs.2018.05.012

Cited by 19 publications

(8 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, much care is not given to HIV patients who have comorbid conditions, thus increasing the risk of ADRs amongst these patients (Labarga et al, 2007 ; Wu et al, 2017 ; Su et al, 2018 ). For example, patients with liver disease and hepatitis may experience enhanced hepatotoxicity due to EFV (Agbaji et al, 2013 ; Wu et al, 2017 ; Nampala et al, 2018 ; Su et al, 2018 ). Certain preexisting conditions, such as mild psychiatric disorder, may be exacerbated by EFV.…”

Section: Population Disparity In the Use Of Cyp2b6 Substrates And Consequent Exposure To Substrate-specific Adverse Drug Reaction (Adr)mentioning

confidence: 99%

CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations—Implication for Drug Safety, Dosing, and Individualized Therapy

et al. 2021

View full text Add to dashboard Cite

Adverse drug reactions (ADRs) are one of the major causes of morbidity and mortality worldwide. It is well-known that individual genetic make-up is one of the causative factors of ADRs. Approximately 14 million single nucleotide polymorphisms (SNPs) are distributed throughout the entire human genome and every patient has a distinct genetic make-up which influences their response to drug therapy. Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of antiretroviral, antimalarial, anticancer, and antidepressant drugs. These drug classes are commonly in use worldwide and face specific population variability in side effects and dosing. Parts of this variability may be caused by single nucleotide polymorphisms (SNPs) in the CYP2B6 gene that are associated with altered protein expression and catalytic function. Population variability in the CYP2B6 gene leads to changes in drug metabolism which may result in adverse drug reactions or therapeutic failure. So far more than 30 non-synonymous variants in CYP2B6 gene have been reported. The occurrence of these variants show intra and interpopulation variability, thus affecting drug efficacy at individual and population level. Differences in disease conditions and affordability of drug therapy further explain why some individuals or populations are more exposed to CYP2B6 pharmacogenomics associated ADRs than others. Variabilities in drug efficacy associated with the pharmacogenomics of CYP2B6 have been reported in various populations. The aim of this review is to highlight reports from various ethnicities that emphasize on the relationship between CYP2B6 pharmacogenomics variability and the occurrence of adverse drug reactions. In vitro and in vivo studies evaluating the catalytic activity of CYP2B6 variants using various substrates will also be discussed. While implementation of pharmacogenomic testing for personalized drug therapy has made big progress, less data on pharmacogenetics of drug safety has been gained in terms of CYP2B6 substrates. Therefore, reviewing the existing evidence on population variability in CYP2B6 and ADR risk profiles suggests that, in addition to other factors, the knowledge on pharmacogenomics of CYP2B6 in patient treatment may be useful for the development of personalized medicine with regards to genotype-based prescription.

show abstract

Section: Population Disparity In the Use Of Cyp2b6 Substrates And Consequent Exposure To Substrate-specific Adverse Drug Reaction (Adr)mentioning

confidence: 99%

CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations—Implication for Drug Safety, Dosing, and Individualized Therapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In their model, the authors did not consider treatment for all infections rather intended only on prevention against HBV infection. Nampala et al [25] formulated an epidemiological model of hepatotoxicity and antiretroviral healing effects in HBV-HIV coinfection. The authors used numerical techniques to study the healing as well as toxic effect of the recently used HBV-HIV therapy, and as a result formulated a desirable combination for treating the effect of HBV and HIV infections.…”

Section: Introductionmentioning

confidence: 99%

Coinfection Dynamics of HBV-HIV/AIDS with Mother-to-Child Transmission and Medical Interventions

Endashaw

Melese

Alemneh

2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

In this study, we analyzed the effect of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) on the transmission dynamics of their coinfection to make a recommendation based on reasons to public health sector, policy makers, and programme implementers. We proved that the solutions of the sub and full models are positive and bounded. The effective reproduction numbers of the models are derived using the next generation matrix method. The disease-free and endemic equilibria of the submodels and the coinfection model are computed, and the stability of those equilibria is analyzed using Routh-Hurwitz criteria after computing the associated effective reproduction numbers. We performed a sensitivity analysis to show the influence of different parameters on the effective reproduction number of HBV-HIV/AIDS coinfection model, and we identified the most sensitive parameters are τ 2 and α 1 , which are the rate of MTCT of HIV and treatment rate for HBV infected class, respectively. The numerical simulation of the model is done using MATLAB and the findings from the simulations are discussed. From the results of numerical simulations, we observed that an increase in the rates of MTCT of HBV and HIV exacerbated HBV-HIV/AIDS coinfection, while a decrease in the rates of MTCT of these infections would decline the number of cases, minimize the spread, and help to eliminate HBV-HIV/AIDS coinfection from the society gradually.

show abstract

“…Journal of Applied Mathematics models on HIV consider viral infection in CD4+ cells. To date, only our previous work in [30][31][32][33] considers the mathematical approach of HIV dynamics in hepatocytes. In this study, we look at the dynamics of HIV/HBV coinfection in human hepatocytes incorporating intracellular delay and antiretroviral therapy.…”

Section: Introductionmentioning

confidence: 99%

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

Nampala

Jabłońska-Sabuka

Singull

2021

Journal of Applied Mathematics

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Modelling hepatotoxicity and antiretroviral therapeutic effect in HIV/HBV coinfection

Cited by 19 publications

References 38 publications

CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations—Implication for Drug Safety, Dosing, and Individualized Therapy

CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations—Implication for Drug Safety, Dosing, and Individualized Therapy

Coinfection Dynamics of HBV-HIV/AIDS with Mother-to-Child Transmission and Medical Interventions

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

Contact Info

Product

Resources

About