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  • 简介:Liverinjuryisacharacteristicfeatureofhumanimmunodeficiencyvirus(HIV)infection,whichisthesecondmostcommoncauseofmortalityinHIV-infectedpatients.NowitisrecognizedthatliverplaysakeyroleinHIVinfectionpathogenesis.Antiretroviraltherapy(ART),whichsuppressesHIVinfectioninpermissiveimmunecells,islesseffectiveinhepatocytes,therebymakingthesecellsasilentreservoirofHIVinfection.InadditiontodirecthepatotoxiceffectsofHIV,certainARTtreatmentmodalitiesprovidehepatotoxiceffects.TheexactmechanismsofHIV-triggeredchronichepatitisprogressionarenotelucidated,buttheliverisadverselyaffectedbyHIV-infectionandlivercellsareprominentlyinvolvedinHIV-elicitedinjury.Theseeffectsarepotentiatedbysecondhitslikealcohol.Here,wewillfocusontheincidenceofHIV,clinicalevidenceofHIVrelatedliverdamage,interactionsbetweenHIVandlivercellsandtheroleofalcoholandco-infectionwithhepatotropicvirusesinliverinflammationandfibrosisprogression.

  • 标签: LIVER cells ANTIRETROVIRAL therapy Apoptosis INFLAMMATION
  • 作者: Wu Zun-You Scott Sarah Robbins
  • 学科: 医药卫生 >
  • 创建时间:2020-08-10
  • 出处:《中华医学杂志(英文版)》 2020年第03期
  • 机构:Division of HIV Prevention, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, United States.,Division of HIV Prevention, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
  • 简介:AbstractThis paper reviews the current epidemics of human immunodeficiency virus (HIV) infection in China, particularly the globally available prevention strategies developed and implemented. This review focuses on HIV prevention measures in general, such as education, testing, and counseling and in specific responses to transmission modes, such as blood safety, harm reduction for people who inject drugs, and condom promotion to reduce sexual transmission. We also assess newly developed prevention measures, such as prevention treatment, pre-exposure prophylaxis, post-exposure prophylaxis, male circumcision, and promising potential future preventions, including microbicides and vaccines. Based on this assessment, we provide recommendations for their implementation in China. We conclude that there is no magic bullet for HIV prevention, particularly sexual transmission of the disease, but only a combination of these prevention strategies can control the HIV epidemic.

  • 标签: Human immunodeficiency virus infection Epidemic Prevention strategies China
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  • 简介:Toinvestigatetheeffectofphotodynamictherapy(PDT)withhematoporphrinmonomethylether(HMME)onbovineimmunodeficiencyvirus(BIV)canprovidethebasistheoryforphotoinactivationofhumanimmunodeficiencyvirus(HIV).ToassesstheprotectionofHMME-PDTonthecelllineCf2ThinfectedwithBIVR29by3-(4,5)-dimethylthiahiazol-2-yl-3,5-di-phenytetrazoliumbromide(MTT)withpowerdensityof5and25mW/cm~2andenergydensityfrom0.6to3J/cm~2.ToobservetheinhibitionofmembranefusionusinganewreportercelllineBIVEbyfluorescencemicroscope.HMME-PDThassignificantprotectanteffectsonCf2Th-BIVR29withbothpowerdensities,especiallyinthegroupofhighpowerdensity.FluorescentmicroscopeshowsthatthereisnosignificantdifferencebetweenthegroupofPDTandcontrol,whichmeansPDTcouldnotinhibittheBIV-mediatedmembranefusion.

  • 标签: 免疫缺陷 病毒 光子动态治疗 能量密度
  • 简介:AbstractBackground:Acinetobacter baumannii (A. baumannii) has become one of the most important opportunistic pathogens inducing nosocomial pneumonia and increasing mortality in critically ill patients recently. The interaction between A. baumannii infection and immune response can influence the prognosis of A. baumannii related pneumonia. The target of the present study was to investigate the role of immunodeficiency in A. baumannii induced pneumonia.Methods:Male BALB/c mice were randomly divided into the normal immunity control (NIC) group, normal immunity infection (NIA) group, immune compromised control (CIC) group, and immune compromised infection (CIA) group (n = 15 for each group). Intraperitoneal injection of cyclophosphamide and intranasal instillation of A. baumannii solution were used to induce compromised immunity and murine pneumonia, respectively. The mice were sacrificed at 6 and 24 h later and the specimens were collected for further tests. Seven-day mortality of mice was also assessed.Results:After A. baumannii stimulation, the recruitment of neutrophils in mice with normal immunity increased sharply (P = 0.030 at 6 h), while there was no significant raise of neutrophil counts in mice with compromised immune condition (P = 0.092 at 6 h, P = 0.772 at 24 h). The Th cell polarization presented with pulmonary interleukin (IL)-4 and interferon (IFN)-γ level in response to the A. baumannii in CIA group were significantly depressed in comparison with in NIA group (IFN-γ: P = 0.003 at 6 h; P = 0.001 at 24 h; IL-4: P < 0.001 at 6 h; P < 0.001 at 24 h). The pulmonary conventional dendritic cell accumulation was even found to be inhibited after A. baumannii infection in immunocompromised mice (P= 0.033). Correspondingly, A. baumannii associated pneumonia in mice with compromised immunity caused more early stage death, more severe histopathological impairment in lung.Conclusion:A. baumannii could frustrate the immune response in immunocompromised conditions, and this reduced immune response is related to more severe lung injury and worse outcome in A. baumannii induced pneumonia.

  • 标签: Acinetobacter baumannii Compromised immunity Dendritic cells Helper T cell Neutrophilic granulocytes Pneumonia
  • 简介:AbstractBackground:Despite almost two decades of well-funded and comprehensive response efforts by the Chinese Government, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) remains a major problem in China. Yet, few studies have recently examined long-term trends in HIV/AIDS prevalence, incidence, and mortality at the national level. This study aimed to determine the prevalence, incidence, and mortality trends for HIV/AIDS over the past 28 years in China.Methods:We conducted a descriptive, epidemiological, secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 data. To evaluate trends in prevalence, incidence, and mortality over the study period from 1990 to 2017, we calculated values for annual percentage change (APC) and corresponding 95% confidence intervals (CIs) using joinpoint regression analysis.Results:A significant increase in HIV/AIDS prevalence was observed for 1990 to 2009 (APC: 10.7; 95% CI: 10.4, 11.0; P < 0.001), and then remained stable for 2009 to 2017 (APC: 0.7; 95% CI: -0.3, 1.7; P = 0.1). A significant increase in HIV incidence was also observed for 1990 to 2005 (APC: 13.0; 95% CI: 12.6, 13.4; P < 0.001), and then a significant decrease was detected for 2005 to 2017 (APC: -6.5; 95% CI: -7.0, -6.1; P < 0.001). A significant increase in AIDS-related mortality rate was detected for 1990 to 2004 (APC: 10.3; 95% CI: 9.3, 11.3; P < 0.001), followed by a period of stability for 2004 to 2013 (APC: 1.3; 95% CI: -0.7, 3.3; P = 0.2), and then another significant increase for 2013 to 2017 (APC: 15.3; 95% CI: 8.7, 22.2; P < 0.001).Conclusions:Although prevalence has stabilized and incidence has declined, AIDS-related mortality has risen sharply in recent years. These findings suggest more must be done to bring people into treatment earlier, retain them in treatment more effectively, actively seek to reenter them in treatment if they dropout, and improve the quality of treatment and care regimens.

  • 标签: Prevalence Incidence Mortality HIV Trend China Acquired immunodeficiency syndrome
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  • 作者: Xu Jun-Jie Shang Hong
  • 学科: 医药卫生 >
  • 创建时间:2021-01-17
  • 出处:《中华医学杂志(英文版)》 2020年第23期
  • 机构:NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China; Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang,
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  • 简介:During2004,atotalof124batchesofHIVantibodyELISAsfromdomesticandoverseasmanufacturers,comprisingapproximately60milliontests,weretestedforqualityandreleasedforscreeningbloodinChina.Theinter-andintra-batchvariation,specificity,andsensitivitywereevaluatedusingalaboratorypanelandclinicalsamples.Theinter-batchvariationwaslessthan15%andonly2of12assayshadintra-batchvariationoflessthan20%for4dilutionsofacontrolspecimen.257samplesconfirmedpositiveforHIVantibodyand4826negativesamplesfromdifferentregionsinChinawereusedtoevaluatethesensitivityandspecificityoftheassays.Theresultsshowedthatthesensitivityisintherangefrom93.7%to100%forassayssampleddirectlyfromthemanufacturers,and91.4%-99.6%forthoseretrievedfromtheconsumers;thespecificitywasintherangefrom97.88%to99.97%.ThetestingenvironmentmayvaryindifferentregionsofChina.Therefore,manufacturersshouldproviderobustassaystosatisfytherequirementsofthesediverseenvironments,andespeciallyreducetheintra-assayvariationandimprovethestabilityofthekits.

  • 标签: 质量控制 免疫缺陷病毒抗体 血液 中国
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  • 简介:AbstractBackground:Cryptococcal meningitis (CM) is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus (HIV)-infected patients, and is complicated with significant morbidity and mortality. This study retrospectively analyzed the clinical features, characteristics, treatment, and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up.Methods:Data from all patients (n = 101) of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality.Results:Of the 101 patients, 86/99 (86.9%) of patients had CD4 count <50 cells/mm3, 57/101 (56.4%) were diagnosed at ≥14 days from the onset to diagnosis, 42/99 (42.4%) had normal cerebrospinal fluid (CSF) cell counts and biochemical examination, 30/101 (29.7%) had concomitant Pneumocystis (carinii) jiroveci pneumonia (PCP) on admission and 37/92 (40.2%) were complicated with cryptococcal pneumonia, 50/74 (67.6%) had abnormalities shown on intracranial imaging, amongst whom 24/50 (48.0%) had more than one lesion. The median time to negative CSF Indian ink staining was 8.50 months (interquartile range, 3.25-12.00 months). Patients who initiated antiretroviral therapy (ART) before admission had a shorter time to negative CSF Indian ink compared with ART-naïve patients (7 vs. 12 months, χ2 = 15.53, P < 0.001). All-cause mortality at 2 weeks, 8 weeks, and 2 years was 10.1% (10/99), 18.9% (18/95), and 20.7% (19/92), respectively. Coinfection with PCP on admission (adjusted odds ratio [AOR], 3.933; 95% confidence interval [CI], 1.166-13.269, P= 0.027) and altered mental status (AOR, 9.574; 95% CI, 2.548-35.974, P = 0.001) were associated with higher mortality at 8 weeks.Conclusion:This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data. Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.

  • 标签: Clinical features Cryptococcal meningitis HIV Intracranial lesions Mortality
  • 简介:AbstractMany seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as "selective elimination of host cells capable of producing HIV" (SECH). Similar to the "shock and kill strategy," the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

  • 标签: HIV SECH Latency reversal Autophagy Apoptosis Cell infection inhibition
  • 简介:AbstractBackground:Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus (HIV). However, little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV (PLHIV). Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab(R-CHOP) as front line therapy for PLHIV with diffuse large B-cell lymphoma (DLBCL) receiving modern combined antiretroviral therapy (cART).Methods:A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019. The demographic and clinical data were collected, and overall survival (OS) and progression-free survival (PFS) analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis. Additionally, a Cox multiple regression model was constructed to identify related factors for OS.Results:A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months (interquartile range [IQR]: 8-29 months). The proportion of high international prognostic index (IPI) patients was much larger in the DA-EPOCH-R group (n = 29) than that in the R-CHOP group (n = 25). The CD4 cell counts and HIV RNA levels were not significantly different between the two groups. The 2-year OS for all patients was 73%. However, OS was not significantly different between the two groups, with a 2-year OS rate of 78% for the DA-EPOCH-R group and 66% for the R-CHOP group. Only an IPI greater than 3 was associated with a decrease in OS, with a hazard ratio of 5.0. The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.Conclusions:Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy. No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.

  • 标签: Diffuse large B-cell lymphoma HIV infection Overall survival Progression free survival
  • 简介:AbstractBackground:Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART).Methods:From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People’s Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (108 cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group.Results:From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P= 0.006) and CD8 level (β = 322.47, P= 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course.Conclusions:This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted.Registration info:www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).

  • 标签: HIV-1 Immune reconstitution Immunological non-responders Immunotherapy Natural killer cell NK cell