In this study,a numerical method based on the Pell-Lucas polynomials(PLPs)is developed to solve the fractional order HIV/AIDS epidemic model with a treatment compartment.The HIV/AIDS mathematical model with a treatmen...In this study,a numerical method based on the Pell-Lucas polynomials(PLPs)is developed to solve the fractional order HIV/AIDS epidemic model with a treatment compartment.The HIV/AIDS mathematical model with a treatment compartment is divided into five classes,namely,susceptible patients(S),HIV-positive individuals(I),individuals with full-blown AIDS but not receiving ARV treatment(A),individuals being treated(T),and individuals who have changed their sexual habits sufficiently(R).According to the method,by utilizing the PLPs and the collocation points,we convert the fractional order HIV/AIDS epidemic model with a treatment compartment into a nonlinear system of the algebraic equations.Also,the error analysis is presented for the Pell-Lucas approximation method.The aim of this study is to observe the behavior of five populations after 200 days when drug treatment is applied to HIV-infectious and full-blown AIDS people.To demonstrate the usefulness of this method,the applications are made on the numerical example with the help of MATLAB.In addition,four cases of the fractional order derivative(p=1,p=0.95,p=0.9,p=0.85)are examined in the range[0,200].Owing to applications,we figured out that the outcomes have quite decent errors.Also,we understand that the errors decrease when the value of N increases.The figures in this study are created in MATLAB.The outcomes indicate that the presented method is reasonably sufficient and correct.展开更多
HIV is a retrovirus that infects and impairs the cells and functions of the immune system. It has caused a great challenge to global public health systems and leads to Acquired Immunodeficiency Syndrome (AIDS), if not...HIV is a retrovirus that infects and impairs the cells and functions of the immune system. It has caused a great challenge to global public health systems and leads to Acquired Immunodeficiency Syndrome (AIDS), if not attended to in good time. Antiretroviral therapy is used for managing the virus in a patient’s lifetime. Some of the symptoms of the disease include lean body mass and many opportunistic infections. This study has developed a SIAT mathematical model to investigate the impact of inconsistency in treatment of the disease. The arising non-linear differential equations have been obtained and analyzed. The DFE and its stability have been obtained and the study found that it is locally asymptotically stable when the basic reproduction number is less than unity. The endemic equilibrium has been obtained and found to be globally asymptotically stable when the basic reproduction number is greater than unity. Numerical solutions have been obtained and analyzed to give the trends in the spread dynamics. The inconsistency in treatment uptake has been analyzed through the numerical solutions. The study found that when the treatment rate of those infected increases, it leads to an increase in treatment population, which slows down the spread of HIV and vice versa. An increase in the rate of treatment of those with AIDS leads to a decrease in the AIDS population, the reverse happens when this rate decreases. The study recommends that the community involvement in advocating for consistent treatment of HIV to curb the spread of the disease.展开更多
A non-linear HIV-TB co-infection has been formulated and analyzed. The positivity and invariant region has been established. The disease free equilibrium and its stability has been determined. The local stability was ...A non-linear HIV-TB co-infection has been formulated and analyzed. The positivity and invariant region has been established. The disease free equilibrium and its stability has been determined. The local stability was determined and found to be stable under given conditions. The basic reproduction number was obtained and according to findings, co-infection diminishes when this number is less than unity, and persists when the number is greater than unity. The global stability of the endemic equilibrium was calculated. The impact of HIV on TB was established as well as the impact of TB on HIV. Numerical solution was also done and the findings indicate that when the rate of HIV treatment increases the latent TB increases while the co-infected population decreases. When the rate of HIV treatment decreases the latent TB population decreases and the co-infected population increases. Encouraging communities to prioritize the consistent treatment of HIV infected individuals must be emphasized in order to reduce the scourge of HIV-TB co-infection.展开更多
Objective This study was to investigate the HIV current situation in Liangshan prefecture, in order to predict prevalence and transmission trends. Methods Region-specific population, behavior, serosurveillence, and po...Objective This study was to investigate the HIV current situation in Liangshan prefecture, in order to predict prevalence and transmission trends. Methods Region-specific population, behavior, serosurveillence, and policy/program data (from 1995 to 2020) were gathered from various local and national organizations and applied to the Asian Epidemic Model (AEM) and used to derive estimates of future HIV prevalence, epidemic trends, and outcomes of intervention strategies. Results The AEM projections for 2020 included increased number of people living with HIV (PLHIV; to 136 617), increased HIV prevalence (2.51%), and 8037 deaths from acquired immunodeficiency syndrome (AIDS) in this region. However, the overall HIV incidence rate (per 10 000) was projected to decline from 27 in 2015 to 22 in 2020, largely due to a predicted decrease in HIV infection rate (per 10 000) from 658 in 2013 to 621 in 2020 among intravenous drug users. In contrast, the cases of HIV infection per i0 000 was projected to increase from 420 in 2010 to 503 in 2020 among men who have sex with men, and from 8 in 2010 to 15 in 2020 among the general population. The predominant risk factor for HIV transmission over the next decade in Liangshan was casual sex. Community-based outreach strategies to reduce injected drug use and casual sex, and to promote condom use, were predicted as effective interventions to decrease HIV transmission. Conclusion Implementation of a comprehensive public health program, with targeting to the region-specific at-risk populations, will help to mitigate HIV/AIDS spread in Liangshan.展开更多
This study explored a novel systemic community-based model for detecting and manag-ing people living with HIV/AIDS (PLWHA). Both quantitative and qualitative research methods were used in this study. A quantitative qu...This study explored a novel systemic community-based model for detecting and manag-ing people living with HIV/AIDS (PLWHA). Both quantitative and qualitative research methods were used in this study. A quantitative questionnaire investigation was conducted in a sample of 1192 subjects which were randomly selected from two areas with high HIV prevalence, Xiangfan City and Shiyan City of Hubei Province, China. Twenty-two medical and health service staffs were inter-viewed by semi-structured questionnaire focusing on awareness, status, problems, and suggestions about community-based Voluntary Counseling and Testing and Provider Initiated Testing and Coun-seling (VCT/PITC). And they were organized to discuss about the aforementioned issues in Xiangfan City and Shiyan City, respectively. Our results showed that the accessibility and availability of the general VCT/PITC were bad. About 28.3% had known and only 4.9% had made use of VCT/PITC. Developing community-based VCT/PITC had some special advantages that can overcome some ex-isting problems to remedy the aforementioned defects. We are led to conclude that, to maximize the availability and uptake rate of the VCT/PITC, we plan to detect PLWHA by developing the commu-nity-based VCT/PITC through 4 paths. Then we establish the community HIV health care center con-stituted of 8 sectors to provide an overall management. Thus, we can effectively detect and manage the PLWHA with a new systemic community-based model.展开更多
HIV/AIDS is a public health problem especially in sub-Saharan Africa where majority of infections and deaths occur. Despite the large number of studies and efforts made in covering the data gap using mathematical mode...HIV/AIDS is a public health problem especially in sub-Saharan Africa where majority of infections and deaths occur. Despite the large number of studies and efforts made in covering the data gap using mathematical models, little is known on how model estimates are confounded by the transmission variabilities that exist in stages of HIV progression. This work investigates the impact of including stages of HIV transmission in HIV/AIDS models. A deterministic HIV/AIDS model is developed and extended to include stages of HIV progression of infected individuals. Theoretical investigation of the models and numerical analyses indicate that the two models produce different estimates, with the model without stages producing lower estimates than the staged model. These results call for a careful consideration in evaluating the efficiency of HIV/AIDS models that are used to estimate and project the burden of HIV/AIDS disease.展开更多
A delayed HIV/AIDS epidemic model with treatment and vertical transmission is investigated. The model allows some infected individuals to move from the symptomatic phase to the asymptomatic phase;next generation of in...A delayed HIV/AIDS epidemic model with treatment and vertical transmission is investigated. The model allows some infected individuals to move from the symptomatic phase to the asymptomatic phase;next generation of infected individuals may be infected and it will take them some time to get maturity and infect others. Mathematical analysis shows that the global dynamics of the spread of the HIV/AIDS are completely determined by the basic reproduction number R0 for our model. If R0 R0 > 1.展开更多
Drug use (DU), particularly injecting drug use (IDU) has been the main route of transmission and spread of Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDSJ among injecting drug use...Drug use (DU), particularly injecting drug use (IDU) has been the main route of transmission and spread of Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDSJ among injecting drug users (IDUs)[1]. Previous studies have proven that needles or cottons sharing during drug injection were major risk factors for HIV/AIDS transmission at the personal level[z4]. Being a social behavioral issue, HIV/AIDS related risk factors should be far beyond the personal level. Therefore, studies on HIV/AIDS related risk factors should focus not only on the individual factors, but also on the association between HIV/AIDS cases and macroscopic-factors, such as economic status, transportation, health care services, etc[1]. The impact of the macroscopic-factors on HIV/AIDS status might be either positive or negative, which are potentially reflected in promoting, delaying or detecting HIV/AIDS epidemics.展开更多
The replication of HIV-1 requires the integration of its cyclic DNA into host DNA by HIV-1 integrase (IN), which includes two important reactions, 3'-processing and strand transfer, both catalyzed by HIV-1 IN. Disr...The replication of HIV-1 requires the integration of its cyclic DNA into host DNA by HIV-1 integrase (IN), which includes two important reactions, 3'-processing and strand transfer, both catalyzed by HIV-1 IN. Disrupting either of the reactions will fulfill the purpose of inhibiting the replication of HIV-1. In this paper, pharmacophore modeling and molecular docking are employed to investigate the inhibition mechanism of the HIV-1 IN strand transfer inhibitors (INSTIs). Based on the results, we suggest that the inhibition mechanism of INSTIs involves the inhibitor chelating the cofactors Mg2+ and its forming hydrogen bonds with some crucial residues adjacent to the DDE active center.展开更多
Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and tr...Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV coinfection or in the basic understanding of the mechanisms for the impairments to the immune system by interactions of these two pathogens. One important reason for these unsolved issues is the lack of appropriate animal models for the study of M.tb/HIV coinfection. This paper reviews the recent development of research on the animal models of M.tb/HIV co-infection, with a focus on the non-human primate models.展开更多
Mycobacterium tuberculosis(MTB) and human immunodeficiency virus(HIV) co-infections have remained a major public health concern worldwide,particularly in Southern Africa.Yet our understanding of the molecular interact...Mycobacterium tuberculosis(MTB) and human immunodeficiency virus(HIV) co-infections have remained a major public health concern worldwide,particularly in Southern Africa.Yet our understanding of the molecular interactions between the pathogens has remained poor,primarily due to lack of suitable preclinical models for such studies.We reviewed the use,this far,of mammalian cell culture models in HIV-MTB interaction studies.Studies have described the use of primary human cell cultures,including monocyte-derived macrophage(MDM) fractions of peripheral blood mononuclear cell(PBMC),alveolar macrophages(AM),cell lines such as the monocyte-derived macrophage cell line(U937),T lymphocyte cell lines(CEMx174,ESAT-6-specific CD4+ T-cells) and an alveolar epithelial cell line(A549) and special models such as stem cells,three dimensional(3D) or organoid cell models [including a blood-brain barrier(BBB) cell model] in HIV-MTB interaction studies.The use of cell cultures from other mammals,including:mouse cell lines [macrophage cell lines RAW 264.7 and J774.2,fibroblast cell lines(NIH 3T3,C3 H clones),embryonic fibroblast cell lines and T-lymphoma cell lines(S1A.TB,TIMI.4 and R1.1)]; rat(T cells:Rat2,RGE,XC and HH16,and alveolar cells:NR8383) and primary guinea pigs derived AMs,in HIV-MTB studies is also described.Given the spectrum of the models available,cell cultures offer great potential for host-HIV-MTB interactions studies.展开更多
A mathematical model describing the antiretroviral therapy of Enfuvirtide on HIV-1 patients is developed. The effect of Enfuvirtide (formerly called T-20) by impulsive differential equations is modeled by two differ...A mathematical model describing the antiretroviral therapy of Enfuvirtide on HIV-1 patients is developed. The effect of Enfuvirtide (formerly called T-20) by impulsive differential equations is modeled by two different drug elimination kinetics, the first-order elimination kinetics and the Michaelis-Menten elimination kinetics. The model is a non-autonomous system of differential equations. For a time-dependent system, the disease-free equilibrium is mainly studied. Its stability, when the therapy is taken with perfect adherence, is obtained. To ensure the disease-free equilibrium remains stable, the analytical thresholds for dosage and dosing intervals are determined. The effects of super- vised treatment interruption are also explored. It is shown that the supervised treatment interruption can be worse than no therapy at all.展开更多
In this paper,an HIV dynamics model with the proliferation of CD4 T cells is proposed.The authors consider nonnegativity,boundedness,global asymptotic stability of the solutions and bifurcation properties of the stead...In this paper,an HIV dynamics model with the proliferation of CD4 T cells is proposed.The authors consider nonnegativity,boundedness,global asymptotic stability of the solutions and bifurcation properties of the steady states.It is proved that the virus is cleared from the host under some conditions if the basic reproduction number R0 is less than unity.Meanwhile,the model exhibits the phenomenon of backward bifurcation.We also obtain one equilibrium is semi-stable by using center manifold theory.It is proved that the endemic equilibrium is globally asymptotically stable under some conditions if R0 is greater than unity.It also is proved that the model undergoes Hopf bifurcation from the endemic equilibrium under some conditions.It is novelty that the model exhibits two famous bifurcations,backward bifurcation and Hopf bifurcation.The model is extended to incorporate the specific Cytotoxic T Lymphocytes(CTLs)immune response.Stabilities of equilibria and Hopf bifurcation are considered accordingly.In addition,some numerical simulations for justifying the theoretical analysis results are also given in paper.展开更多
The aim of this study is to develop two-dimensional cellular automata model of HIV infection that depicts the dynamics involved in the interactions between acquired immune system and HIV infection in the peripheral bl...The aim of this study is to develop two-dimensional cellular automata model of HIV infection that depicts the dynamics involved in the interactions between acquired immune system and HIV infection in the peripheral blood stream. The appropriate biological rules of cellular automata model have been extracted from expert knowledge and the model has been simulated with determined initial conditions. Obtained results have been validated through comparing with the accepted AIDS reference curve. The new rules and states were added to the proposed model to show the effects of applying combined antiretroviral therapy. Our results showed that by applying RTI and PI drugs with maximum drug effectiveness, comparing with cases in which no treatment was applied, the steady state concentrations of healthy (infected) CD4+T cells were increased (decreased) 53% (41%). Also, the use of cART with maximum drug effectiveness led to a 69% reduction in the steady state level of viral load. At this time, obtained results have been validated through comparing with available clinical data. Our results showed good agreement with both reference curve and the clinical data. In the second phase of this study, by applying genetic algorithms, a therapeutic schedule has been provided that its use, while maintaining the quality of the treatment, leads to a 47% reduction in both drug dosage and the side effects of antiretroviral drugs.展开更多
文摘In this study,a numerical method based on the Pell-Lucas polynomials(PLPs)is developed to solve the fractional order HIV/AIDS epidemic model with a treatment compartment.The HIV/AIDS mathematical model with a treatment compartment is divided into five classes,namely,susceptible patients(S),HIV-positive individuals(I),individuals with full-blown AIDS but not receiving ARV treatment(A),individuals being treated(T),and individuals who have changed their sexual habits sufficiently(R).According to the method,by utilizing the PLPs and the collocation points,we convert the fractional order HIV/AIDS epidemic model with a treatment compartment into a nonlinear system of the algebraic equations.Also,the error analysis is presented for the Pell-Lucas approximation method.The aim of this study is to observe the behavior of five populations after 200 days when drug treatment is applied to HIV-infectious and full-blown AIDS people.To demonstrate the usefulness of this method,the applications are made on the numerical example with the help of MATLAB.In addition,four cases of the fractional order derivative(p=1,p=0.95,p=0.9,p=0.85)are examined in the range[0,200].Owing to applications,we figured out that the outcomes have quite decent errors.Also,we understand that the errors decrease when the value of N increases.The figures in this study are created in MATLAB.The outcomes indicate that the presented method is reasonably sufficient and correct.
文摘HIV is a retrovirus that infects and impairs the cells and functions of the immune system. It has caused a great challenge to global public health systems and leads to Acquired Immunodeficiency Syndrome (AIDS), if not attended to in good time. Antiretroviral therapy is used for managing the virus in a patient’s lifetime. Some of the symptoms of the disease include lean body mass and many opportunistic infections. This study has developed a SIAT mathematical model to investigate the impact of inconsistency in treatment of the disease. The arising non-linear differential equations have been obtained and analyzed. The DFE and its stability have been obtained and the study found that it is locally asymptotically stable when the basic reproduction number is less than unity. The endemic equilibrium has been obtained and found to be globally asymptotically stable when the basic reproduction number is greater than unity. Numerical solutions have been obtained and analyzed to give the trends in the spread dynamics. The inconsistency in treatment uptake has been analyzed through the numerical solutions. The study found that when the treatment rate of those infected increases, it leads to an increase in treatment population, which slows down the spread of HIV and vice versa. An increase in the rate of treatment of those with AIDS leads to a decrease in the AIDS population, the reverse happens when this rate decreases. The study recommends that the community involvement in advocating for consistent treatment of HIV to curb the spread of the disease.
文摘A non-linear HIV-TB co-infection has been formulated and analyzed. The positivity and invariant region has been established. The disease free equilibrium and its stability has been determined. The local stability was determined and found to be stable under given conditions. The basic reproduction number was obtained and according to findings, co-infection diminishes when this number is less than unity, and persists when the number is greater than unity. The global stability of the endemic equilibrium was calculated. The impact of HIV on TB was established as well as the impact of TB on HIV. Numerical solution was also done and the findings indicate that when the rate of HIV treatment increases the latent TB increases while the co-infected population decreases. When the rate of HIV treatment decreases the latent TB population decreases and the co-infected population increases. Encouraging communities to prioritize the consistent treatment of HIV infected individuals must be emphasized in order to reduce the scourge of HIV-TB co-infection.
基金funded by China-MSD HIV/AIDS Partnership Project(2012-83)Comprehensive Assessment for HIV/AIDS Control and Prevention in Sichuan Province Project(2006-2010)
文摘Objective This study was to investigate the HIV current situation in Liangshan prefecture, in order to predict prevalence and transmission trends. Methods Region-specific population, behavior, serosurveillence, and policy/program data (from 1995 to 2020) were gathered from various local and national organizations and applied to the Asian Epidemic Model (AEM) and used to derive estimates of future HIV prevalence, epidemic trends, and outcomes of intervention strategies. Results The AEM projections for 2020 included increased number of people living with HIV (PLHIV; to 136 617), increased HIV prevalence (2.51%), and 8037 deaths from acquired immunodeficiency syndrome (AIDS) in this region. However, the overall HIV incidence rate (per 10 000) was projected to decline from 27 in 2015 to 22 in 2020, largely due to a predicted decrease in HIV infection rate (per 10 000) from 658 in 2013 to 621 in 2020 among intravenous drug users. In contrast, the cases of HIV infection per i0 000 was projected to increase from 420 in 2010 to 503 in 2020 among men who have sex with men, and from 8 in 2010 to 15 in 2020 among the general population. The predominant risk factor for HIV transmission over the next decade in Liangshan was casual sex. Community-based outreach strategies to reduce injected drug use and casual sex, and to promote condom use, were predicted as effective interventions to decrease HIV transmission. Conclusion Implementation of a comprehensive public health program, with targeting to the region-specific at-risk populations, will help to mitigate HIV/AIDS spread in Liangshan.
基金supported by a grant from the Global Fund(No. 2008-NGS-26)
文摘This study explored a novel systemic community-based model for detecting and manag-ing people living with HIV/AIDS (PLWHA). Both quantitative and qualitative research methods were used in this study. A quantitative questionnaire investigation was conducted in a sample of 1192 subjects which were randomly selected from two areas with high HIV prevalence, Xiangfan City and Shiyan City of Hubei Province, China. Twenty-two medical and health service staffs were inter-viewed by semi-structured questionnaire focusing on awareness, status, problems, and suggestions about community-based Voluntary Counseling and Testing and Provider Initiated Testing and Coun-seling (VCT/PITC). And they were organized to discuss about the aforementioned issues in Xiangfan City and Shiyan City, respectively. Our results showed that the accessibility and availability of the general VCT/PITC were bad. About 28.3% had known and only 4.9% had made use of VCT/PITC. Developing community-based VCT/PITC had some special advantages that can overcome some ex-isting problems to remedy the aforementioned defects. We are led to conclude that, to maximize the availability and uptake rate of the VCT/PITC, we plan to detect PLWHA by developing the commu-nity-based VCT/PITC through 4 paths. Then we establish the community HIV health care center con-stituted of 8 sectors to provide an overall management. Thus, we can effectively detect and manage the PLWHA with a new systemic community-based model.
文摘HIV/AIDS is a public health problem especially in sub-Saharan Africa where majority of infections and deaths occur. Despite the large number of studies and efforts made in covering the data gap using mathematical models, little is known on how model estimates are confounded by the transmission variabilities that exist in stages of HIV progression. This work investigates the impact of including stages of HIV transmission in HIV/AIDS models. A deterministic HIV/AIDS model is developed and extended to include stages of HIV progression of infected individuals. Theoretical investigation of the models and numerical analyses indicate that the two models produce different estimates, with the model without stages producing lower estimates than the staged model. These results call for a careful consideration in evaluating the efficiency of HIV/AIDS models that are used to estimate and project the burden of HIV/AIDS disease.
文摘A delayed HIV/AIDS epidemic model with treatment and vertical transmission is investigated. The model allows some infected individuals to move from the symptomatic phase to the asymptomatic phase;next generation of infected individuals may be infected and it will take them some time to get maturity and infect others. Mathematical analysis shows that the global dynamics of the spread of the HIV/AIDS are completely determined by the basic reproduction number R0 for our model. If R0 R0 > 1.
基金supported by the National Scientific Research Mega-Project under the 12th Five-Year Plan of China(2012ZX10001001)
文摘Drug use (DU), particularly injecting drug use (IDU) has been the main route of transmission and spread of Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDSJ among injecting drug users (IDUs)[1]. Previous studies have proven that needles or cottons sharing during drug injection were major risk factors for HIV/AIDS transmission at the personal level[z4]. Being a social behavioral issue, HIV/AIDS related risk factors should be far beyond the personal level. Therefore, studies on HIV/AIDS related risk factors should focus not only on the individual factors, but also on the association between HIV/AIDS cases and macroscopic-factors, such as economic status, transportation, health care services, etc[1]. The impact of the macroscopic-factors on HIV/AIDS status might be either positive or negative, which are potentially reflected in promoting, delaying or detecting HIV/AIDS epidemics.
基金supported by the National Natural Science Foundation of China (No. 30472166)the Tianjin Commission of Science and Technology (06YFGZSH07000)
文摘The replication of HIV-1 requires the integration of its cyclic DNA into host DNA by HIV-1 integrase (IN), which includes two important reactions, 3'-processing and strand transfer, both catalyzed by HIV-1 IN. Disrupting either of the reactions will fulfill the purpose of inhibiting the replication of HIV-1. In this paper, pharmacophore modeling and molecular docking are employed to investigate the inhibition mechanism of the HIV-1 IN strand transfer inhibitors (INSTIs). Based on the results, we suggest that the inhibition mechanism of INSTIs involves the inhibitor chelating the cofactors Mg2+ and its forming hydrogen bonds with some crucial residues adjacent to the DDE active center.
基金supported by grants from the National Natural Sciences Foundation of China(81201261,81301428)the National Science Foundation for Post-doctoral Scientists of China(2013M5317456)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2012ZX10004501-001-004)
文摘Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV coinfection or in the basic understanding of the mechanisms for the impairments to the immune system by interactions of these two pathogens. One important reason for these unsolved issues is the lack of appropriate animal models for the study of M.tb/HIV coinfection. This paper reviews the recent development of research on the animal models of M.tb/HIV co-infection, with a focus on the non-human primate models.
基金funded by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa,award number UID 86539
文摘Mycobacterium tuberculosis(MTB) and human immunodeficiency virus(HIV) co-infections have remained a major public health concern worldwide,particularly in Southern Africa.Yet our understanding of the molecular interactions between the pathogens has remained poor,primarily due to lack of suitable preclinical models for such studies.We reviewed the use,this far,of mammalian cell culture models in HIV-MTB interaction studies.Studies have described the use of primary human cell cultures,including monocyte-derived macrophage(MDM) fractions of peripheral blood mononuclear cell(PBMC),alveolar macrophages(AM),cell lines such as the monocyte-derived macrophage cell line(U937),T lymphocyte cell lines(CEMx174,ESAT-6-specific CD4+ T-cells) and an alveolar epithelial cell line(A549) and special models such as stem cells,three dimensional(3D) or organoid cell models [including a blood-brain barrier(BBB) cell model] in HIV-MTB interaction studies.The use of cell cultures from other mammals,including:mouse cell lines [macrophage cell lines RAW 264.7 and J774.2,fibroblast cell lines(NIH 3T3,C3 H clones),embryonic fibroblast cell lines and T-lymphoma cell lines(S1A.TB,TIMI.4 and R1.1)]; rat(T cells:Rat2,RGE,XC and HH16,and alveolar cells:NR8383) and primary guinea pigs derived AMs,in HIV-MTB studies is also described.Given the spectrum of the models available,cell cultures offer great potential for host-HIV-MTB interactions studies.
基金supported by the National Natural Science Foundation of China(No.11072136)the Shanghai Leading Academic Discipline Project(No.S30104)+2 种基金the International Development Research Center of Canada(No.104519-010)the Ministry of Health of China(No.2009DFB30420)the State Key Laboratory for Infectious Disease Prevention and Control of China(No.2008SKLID101)
文摘A mathematical model describing the antiretroviral therapy of Enfuvirtide on HIV-1 patients is developed. The effect of Enfuvirtide (formerly called T-20) by impulsive differential equations is modeled by two different drug elimination kinetics, the first-order elimination kinetics and the Michaelis-Menten elimination kinetics. The model is a non-autonomous system of differential equations. For a time-dependent system, the disease-free equilibrium is mainly studied. Its stability, when the therapy is taken with perfect adherence, is obtained. To ensure the disease-free equilibrium remains stable, the analytical thresholds for dosage and dosing intervals are determined. The effects of super- vised treatment interruption are also explored. It is shown that the supervised treatment interruption can be worse than no therapy at all.
基金The Teacher Research Capacity Promotion Program of Beijing Normal University Zhuhaithe NSF(11871108)of China
文摘In this paper,an HIV dynamics model with the proliferation of CD4 T cells is proposed.The authors consider nonnegativity,boundedness,global asymptotic stability of the solutions and bifurcation properties of the steady states.It is proved that the virus is cleared from the host under some conditions if the basic reproduction number R0 is less than unity.Meanwhile,the model exhibits the phenomenon of backward bifurcation.We also obtain one equilibrium is semi-stable by using center manifold theory.It is proved that the endemic equilibrium is globally asymptotically stable under some conditions if R0 is greater than unity.It also is proved that the model undergoes Hopf bifurcation from the endemic equilibrium under some conditions.It is novelty that the model exhibits two famous bifurcations,backward bifurcation and Hopf bifurcation.The model is extended to incorporate the specific Cytotoxic T Lymphocytes(CTLs)immune response.Stabilities of equilibria and Hopf bifurcation are considered accordingly.In addition,some numerical simulations for justifying the theoretical analysis results are also given in paper.
文摘The aim of this study is to develop two-dimensional cellular automata model of HIV infection that depicts the dynamics involved in the interactions between acquired immune system and HIV infection in the peripheral blood stream. The appropriate biological rules of cellular automata model have been extracted from expert knowledge and the model has been simulated with determined initial conditions. Obtained results have been validated through comparing with the accepted AIDS reference curve. The new rules and states were added to the proposed model to show the effects of applying combined antiretroviral therapy. Our results showed that by applying RTI and PI drugs with maximum drug effectiveness, comparing with cases in which no treatment was applied, the steady state concentrations of healthy (infected) CD4+T cells were increased (decreased) 53% (41%). Also, the use of cART with maximum drug effectiveness led to a 69% reduction in the steady state level of viral load. At this time, obtained results have been validated through comparing with available clinical data. Our results showed good agreement with both reference curve and the clinical data. In the second phase of this study, by applying genetic algorithms, a therapeutic schedule has been provided that its use, while maintaining the quality of the treatment, leads to a 47% reduction in both drug dosage and the side effects of antiretroviral drugs.