A Mother-to-Child Transmission Study in Nigeria: The Impact of Maternal HIV Infection and HAART on Plasma Immunoglobulins,Cytokine Profiles and Infant Outcome

Prevention of mother-to-child transmission (PMTCT) of HIV with highly active antiretroviral therapy (HARRT) allows the HIV~+ pregnant mothers to have vaginal delivery and breastfeed.Here we investigated the maternal plasma immunoglobulin,cytokine secretion and the outcome of the exposed infants among the HIV~+ HAART treated pregnan women in Nigeria.In this study,different plasma immunoglobulins and cytokines were measured in the HIV~+ HAART treated pregnant mothers.Pooled culture supernatants of B and T lymphocytes showed lower levels of IFN-γ,IL-10 and IL-4.There were lower IFN-γ and IL-10 secretions at 1st trimester;however,IL-10 continued to be lower throughout 2nd and 3rd trimesters.TNF-α secretion significantly decreased as pregnancy progressed to term.There were high plasma IgG and low IgM in the HIV~+ HAART treated pregnant women.Plasma IgG was high during 1st and 3rd trimesters.After one year of follow up,all the exposed children were seronegative for HIV-1 and HIV-2.Vaginal delivery and breastfeeding among HIV~+ HAART treated mothers have shown to be safe.The use of HAART by the infected mothers and the use of septrin and niverapin by the exposed infants prevented mother to-child transmission of HIV.     

On transient effects in the HIV/AIDS epidemic

During the initially exponential spread of the human immunodeficiency virus (HIV—the causative agent of AIDS) the growth rate of the number of AIDS cases decreases from plus infinity to the growth rate of HIV infections. A sensitivity analysis shows that for all reasonable values of the parameters of the HIV epidemic (incubation period, initial doubling time, etc.) the effect of this positive transient becomes negligible when the annual number of AIDS cases reaches a few dozen. Necessary and sufficient conditions are given for the growth rate of the number of AIDS cases to be monotonically decreasing during the positive transient. A mildly pathological density function for the incubation period of AIDS provides an example of a growth rate of AIDS that does not decrease monotonically, even though HIV is spreading exponentially. A negative transient occurs when the growth rate of HIV begins to decrease. In this context a somewhat surprising result emerges under the assumption that the growth rate of HIV is non-increasing: the growth rate of AIDS is at all times larger than the growth rate of HIV. A logistic HIV epidemic illustrates this result, and implications for the growth of the HIV epidemic in the United States and Europe are discussed. In particular, it is shown that the positive transient must have passed by 1982 in the United States and by 1986 or 1987 for the five European countries with the largest caseloads.     

43 例HIV/AIDS 患者抗病毒治疗情况分析

目的:研究来第四军医大学唐都医院传染科就诊的人类免疫缺陷病毒/艾滋病(Human immunodeficiency virus/Acquired immuno deficiency syndrome,HIV/AIDS)患者感染状况及抗病毒治疗效果。方法:采用前瞻性随访研究的方法,收集来我院就诊的HIV/AIDS患者的基本信息,并对其实验室检查结果、治疗方案及后续随访结果进行分析。结果:随访观察的43例HIV/AIDS患者治疗前平均基线CD4+T淋巴细胞计数为(330.74±176.35)cells/μL,CD8+T淋巴细胞计数为(1177.80±321.49)cells/μL,CD4+,CD8+T淋巴细胞比值为0.30±0.19;治疗一年后平均CD4+T淋巴细胞计数为(482.74±217.77)cells/μL,CD8+T淋巴细胞计数为(861.53±282.85)cells/μL,CD4+,CD8+T淋巴细胞比值为0.59±0.28。所有患者治疗一年后血浆HIV-RNA载量均达到检测限以下(500copies/m L)。结论:规范的抗病毒治疗对于改善HIV/AIDS患者预后至关重要;基线CD4+T淋巴细胞计数越低,抗病毒治疗效果越差。     

接受高效抗逆转录病毒治疗的 HIV/AIDS患者血浆IL 35及其受体水平的动态变化

目的 检测接受高效抗逆转录病毒治疗(HAART)的人类免疫缺陷病毒(HIV)感染者/艾滋病(AIDS)患者血浆中白介素(IL) 35及其受体IL12rβ2、糖蛋白130(gp130)水平的动态变化及意义。 方法 选择我院2017年1月至2018年3月收治的41例HIV感染者/AIDS患者为研究对象,选择45例同期健康体检者为对照组。分别采集HIV/AIDS患者接受HAART药物0、1、6、12个月时的外周静脉血,检测血浆中的IL 35及其受体IL12rβ2、gp130水平,同时检测血浆HIV 1 RNA载量,分析IL 35与IL12rβ2、gp130、HIV 1 RNA以及IL12rβ2、gp130与HIV 1 RNA病毒载量的相关性。 结果 与对照组相比,接受HAART(0、1、6个月)时患者血浆中IL 35、IL12rβ2、gp130水平降低(均P结论 接受HAART的HIV/AIDS患者血浆IL 35及其受体IL12rβ2、gp130水平随着接受HAART时间的延长而逐渐升高,且与HIV 1 RNA载量关系密切。血浆IL 35及其受体IL12rβ2、gp130在抗HIV感染中可能发挥一定作用。     

Analysis of recruitment and industrial human resources management for optimal productivity in the presence of the HIV/AIDS epidemic

The aim of this paper is to analyze the recruitment effects of susceptible and infected individuals in order to assess the productivity of an organizational labor force in the presence of HIV/AIDS with preventive and HAART treatment measures in enhancing the workforce output. We consider constant controls as well as time-dependent controls. In the constant control case, we calculate the basic reproduction number and investigate the existence and stability of equilibria. The model is found to exhibit backward and Hopf bifurcations, implying that for the disease to be eradicated, the basic reproductive number must be below a critical value of less than one. We also investigate, by calculating sensitivity indices, the sensitivity of the basic reproductive number to the model’s parameters. In the time-dependent control case, we use Pontryagin’s maximum principle to derive necessary conditions for the optimal control of the disease. Finally, numerical simulations are performed to illustrate the analytical results. The cost-effectiveness analysis results show that optimal efforts on recruitment (HIV screening of applicants, etc.) is not the most cost-effective strategy to enhance productivity in the organizational labor force. Hence, to enhance employees’ productivity, effective education programs and strict adherence to preventive measures should be promoted.     

A modeled time-varying density function for the incubation period of AIDS

Building on the Weibull distribution, we develop a modeled time-varying density function of the incubation time between exposure to HIV infection and full-blown AIDS. This approach leads to a series of cohort-specific density functions that take into account the increasing impact of new therapies such as zidovudine (AZT). The resulting modeled density functions are studied in detail, particularly with regard to their modes and medians. The mode is sensitive to changes in the period incubation time distribution, with even a possibility of a bimodal distribution for certain combinations of the parameters that determine the rate at which the period median incubation time changes. An important substantive result is that when a period median incubation period slowly increases to some leveling off value, say m(x _c ), then it is surprisingly early on that cohorts of infected individuals have a median incubation period very close to that ultimate value m(x _c ).     

HIV and HCV: from Co-infection to epidemiology, transmission, pathogenesis, and treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immunodeficiency syndrome (AIDS), a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide, resulting in a serious public health burden. Due to shared routes of transmission, co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease, particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial, most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely, HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications, co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review, we focus on the epidemiology and transmission of HIV and HCV, the impact of the two viruses on each other, and their treatment.      

HIV and HCV： from Co-infection to Epidemiology, Transmission, Pathogenesis, and Treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immu-nodeficiency syndrome (AIDS),a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission,co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease,particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely,HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications,co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review,we focus on the epidemiology and transmission of HIV and HCV,the impact of the two viruses on each other,and their treatment.     

HIV(+)/AIDS并发肺结核与单纯肺结核患者临床对照分析

提高对HIV(+)/AIDS并发肺结核临床表现的认识。方法:选取1998年以来我院收治的HIV(+)/AIDS并发肺结核的病例共47例为观察组(A组),及同期住院的HIV(-)单纯肺结核病例50例为对照组(B组)进行回顾性对照分析。结果:(1)A组发烧和体重下降较B组更常见,而咳嗽和咯血较B组少见;(2)A组痰抗酸杆菌阳性率显著低于B组;(3)A组结核杆菌培养阳性率显著低于B组,而耐多药结核(MDR-TB)所占比率显著高于B组;(4)肺结核的X线表现为弥漫性浸润或粟粒性阴影的,A组多于B组,而A组影像学空洞率显著低于B组;(5)A组合并肺外结核较B组多见,A组淋巴系统较B组常发生结核病变,A组全身血液播散性结核病的发病率明显高于B组;(6)PPD结核菌素反应阳性率A组显著低于B组,A组PPD阳性率与外周CD4+T淋巴细胞数相关。结论:HIV(+)/AIDS患者并发肺结核临床表现不典型。     

Development and challenge of HIV/AIDS testing laboratory network and quality assurance system in China

This paper describes the development and challenge of HIV/AIDS testing laboratory network and quality assurance system in China. At present, the HIV/AIDS testing laboratories includes three classes, the National AIDS Reference Laboratory, HIV/AIDS confirmatory laboratories and HIV/AIDS screening laboratories. All of them are accredited by the health authorities, and each class of laboratories take charge of their function strictly according to the “National Management of HIV/AIDS Detection (2006)”. A complete quality assurance and quality control system for HIV/AIDS testing has been developed, which includes technical training, strict laboratory monitoring and approval, examination or proficiency testing on HIV/AIDS detection, and quality evaluation and supervision of HIV/AIDS diagnostic kits. Besides conduct the routine anti-HIV antibody test, more and more laboratories began to conduct other tests, such as CD4⁺T lymphocyte cell counting, HIV viral load, HIV DNA PCR, genotyping, drug resistance, and HIV-1 recent infection test. The primary challenges faced by the HIV/AIDS testing laboratory network are in the areas of laboratory management and quality control. For example, the provincial PT program is inefficient, the internal quality control is conducted perfunctorily, personnel training can not met the needs of the workplace, which need to be improved. Foundation item: MOH Program on Applied Research in the Prevention and Treatment of AIDS (WA 2003-17)     

Development and Challenge of HIV/AIDS Testing Laboratory Network and Quality Assurance System in China

This paper describes the development and challenge of HIV/AIDS testing laboratory network and quality assurance system in China. At present,the HIV/AIDS testing laboratories includes three classes,the National AIDS Reference Laboratory,HIV/AIDS confirmatory laboratories and HIV/AIDS screening laboratories. All of them are accredited by the health authorities,and each class of laboratories take charge of their function strictly according to the "National Management of HIV/AIDS Detection (2006)". A complete quality assurance and quality control system for HIV/AIDS testing has been developed,which includes technical training,strict laboratory monitoring and approval,examination or proficiency testing on HIV/AIDS detection,and quality evaluation and supervision of HIV/AIDS diagnostic kits. Besides conduct the routine anti-HIV antibody test,more and more laboratories began to conduct other tests,such as CD4 T lymphocyte cell counting,HIV viral load,HIV DNA PCR,genotyping,drug resistance,and HIV-1 recent infection test. The primary challenges faced by the HIV/AIDS testing laboratory network are in the areas of laboratory management and quality control. For example,the provincial PT program is inefficient,the internal quality control is conducted perfunctorily,personnel training can not met the needs of the workplace,which need to be improved.     

Granulocyte-Macrophage Colony-Stimulating Factor and Tumor Necrosis Factor Alpha in Patients with Human Immunodeficiency Virus (HIV) Type 1 Infection

Variations in cytokine production in patients with human immunodeficiency virus (HIV) infection could be involved in the physiopathology and in the progression of the disease. Therefore we studied the level of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor α (TNFα) produced in patients with HIV infection at stage II (asymptomatic seropositives) and stage IV (AIDS) of the CDC classification, by using an enzyme amplified sensitivity immunoassay. We measured the level of GM-CSF and TNFα in supernatant of phytohemagglutinin-activated peripheral blood mononuclear cells from patients and healthy individuals. In one out of 10 stage II patients and 4 out of 14 stage IV patients, we obtained higher levels of GM-CSF than the mean + 2 S.D. of controls, but in 3 stage IV patients with very low CD4+ T lymphocyte counts (< 50/mm^–3) compared to other patients, the GM-CSF values were very low. High levels of TNFα were detected in 3 out of 10 stage II and 6 out of 11 stage IV patients. The high values of TNFα were associated with high values of GM-CSF in stage II and in most of AIDS patients except those with very low CD4⁺ T cell counts, who produced low levels of GM-CSF. Plasma levels of cytokines were evaluated in 10 stage II, 22 stage IV patients and 20 controls. Increased levels of GM-CSF (more than 9 pg/ml) were observed in the plasma from 8 out of 10 stage II patients and 17 out of 22 stage IV patients. The tendency that increased levels of GM-CSF were associated with increased levels of TNFα was observed in plasma from stage IV patients. We report a disarray of GM-CSF production in patients with HIV infection that could be involved in clinical manifestations and progression of the disease.     

On the role of long incubation periods in the dynamics of acquired immunodeficiency syndrome (AIDS)

In this study, we investigate systematically the role played by the reproductive number (the number of secondary infections generated by an infectious individual in a population of susceptibles) on single group populations models of the spread of HIV/AIDS. Our results for a single group model show that if R 1, the disease will die out, and strongly suggest that if R > 1 the disease will persist regardless of initial conditions. Our extensive (but incomplete) mathematical analysis and the numerical simulations of various research groups support the conclusion that the reproductive number R is a global bifurcation parameter. The bifurcation that takes place as R is varied is a transcritical bifurcation; in other words, when R crosses 1 there is a global transfer of stability from the infection-free state to the endemic equilibrium, and vice versa. These results do not depend on the distribution of times spent in the infectious categories (the survivorship functions). Furthermore, by keeping all the key statistics fixed, we can compare two extremes: exponential survivorship versus piecewise constant survivorship (individuals remain infectious for a fixed length of time). By choosing some realistic parameters we can see (at least in these cases) that the reproductive numbers corresponding to these two extreme cases do not differ significantly whenever the two distributions have the same mean. At any rate a formula is provided that allows us to estimate the role played by the survivorship function (and hence the incubation period) in the global dynamics of HIV. These results support the conclusion that single population models of this type are robust and hence are good building blocks for the construction of multiple group models. Our understanding of the dynamics of HIV in the context of mathematical models for multiple groups is critical to our understanding of the dynamics of HIV in a highly heterogeneous population.     

HIV感染者/AIDS病人高迁移率族蛋白1的表达及其临床意义

通过检测74例处于不同病期的HIV感染者/AIDS患者和10例健康对照者PBMCs中HMGB1 mRNA的表达水平及其外周血浆HMGB1、TNF-a和IL-2水平,比较各组之间表达水平的差异及其与CD4＋T淋巴细胞的关系.发现HMGB1 mRNA的表达水平及血浆HMGB1含量在AIDS病人组明显高于感染者组和正常对照组（P〈0.05）;AIDS患者经HAART治疗后疗效差组HMGB1 mRNA的表达水平及血浆HMGB1含量也明显高于疗效好组（P〈0.05）;而经HAART治疗后效果好且免疫功能恢复的患者HMGB1 mRNA的表达及血浆HMGB1含量均较治疗前明显下降（P〈0.05）;当CD4＋T细胞数低于200/μL时,血浆HMGB1含量以及PBMCs中HMGB1 mRNA表达水平与CD4＋T细胞数呈负相关.显示HMGB1在HIV/AIDS发病及病情进展过程中可能起重要作用,HMGB1血浆含量及PBMCs中HMGB1 mRNA的表达水平高低与HIV/AIDS患者病情轻重密切相关.     

艾滋病患者CD4+T细胞基线值与长期高效抗逆转录病毒治疗免疫重建效果的相关性研究

目的:探讨艾滋病患者CD4~+T细胞基线值与长期高效抗逆转录病毒治疗免疫重建效果的相关性。方法:挑选进行长期高效抗逆转录病毒治疗的艾滋病患者120例,并按CD4~+T淋巴细胞计数基线值分为A组(≤100·μL~(-1))共66例和B组(100·μL~(-1))共54例,对两组患者的CD4~+T以及CD8~+T淋巴细胞计数变化进行定期观察以及统计分析。结果:经抗病毒治疗后,B组患者各个阶段的CD4~+T淋巴细胞计数回升水平明显优于A组,差异具有统计学意义(均P0.001);9个月内,B组CD4~+T淋巴细胞计数回升明显优于A组,差异具有统计学意义(P=0.003,P0.001,P=0.002);12个月后,两组患者CD4~+T淋巴细胞计数增幅并无明显差异,无统计学意义(P=0.061,P=0.219,P=0.738);经抗病毒治疗后,两组组患者各个阶段的CD8~+T淋巴细胞计数回升水平均无明显差异,无统计学意义(P=0.447,P=0.681,P=0.639,P=0.464,P=0.886,P=0.712)。结论:艾滋病患者免疫重建受CD4~+T淋巴细胞基线高低的直接影响,而CD8~+T淋巴细胞计数的回升相对较为缓慢。     

A general introduction of HIV/AIDS treatment with Traditional Chinese Medicine in China

This paper gives a general introduction of HIV/AIDS treatment with Traditional Chinese Medicine (TCM) in China during the past 20 years. Although the role of TCM in treatment of HIV/AIDS is promising, there is still a long way to go.      

The role of HIV replicative fitness in perinatal transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selective pressure in the perinatal transmission of HIV-1 is maternal neutralizing antibodies.Recent studies have shown that viruses which are successfully transmitted to the child have growth advantages over those not transmitted,when those two viruses are grown together.Furthermore,the higher fitness is determined by the gp120 protein of the virus envelope.This suggests that the selective transmission of viruses with higher fitness occurred exclusively,regardless of transmission routes.There are many factors contributing to the selective transmission and HIV replicative fitness is an important one that should not be neglected.This review summarizes current knowledge of the role of HIV replicative fitness in HIV MTCT transmission and the determinants of viral fitness upon MTCT.     

A General Introduction of HIV/AIDS Treatment with Traditional Chinese Medicine in China

This paper gives a general introduction of HIV/AIDS treatment with Traditional Chinese Medicine (TCM) in China during the past 20 years. Although the role of TCM in treatment of HIV/AIDS is promising,there is still a long way to go.     

Advance in treatment strategy and immune reconstruction against HIV-1 infection

HIV-1 can be considered an infection of the immune system, resulting in progressive and ultimately profound immune suppression. The availability of highly active antiretroviral therapy (HAART) has resulted in dramatic changes in the disease course in persons fortunate enough to have access to these medications, but long-term therapy is limited by the development of resistance as well as toxicities of the potent medication regimens. Emerging data indicate that individuals who have non-progressive clinical course control HIV-1 immunologically. This has bolstered hope that the immune response might be effectively augmented in persons with HIV infection. Recent data indicating that immediate treatment of acute infection leads to augmentation of antiviral immune responses have provided evidence that the immune system might be enhanced in certain situations. Therefore, investigation in the reconstitution of anti-HIV immune response in patients under HAART should provide encouragement for continuing to explore methods to obtain meaningful and durable immune enhancement as an adjunct to HAART in HIV-1 infection.     

The Role of HIV Replicative Fitness in Perinatal Transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selectiv...