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Candida vertebral osteomyelitis,a rare but challenging clinical disease without specific clinical manifestations,is prone to delay in diagnosis,with potential risks of serious complications.Therefore,early diagnosis is the key to improving the cure rate of this disease.A case of invasive candida lumbar osteomyelitis after gastrointestinal surgery is reported in this paper.We analyzed the clinical characteristics of the patient and reviewed the relevant literature,aiming to improve the early diagnosis and treatment of this disease.
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Candidíase , Osteomielite , Candida , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Humanos , Vértebras Lombares , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológicoRESUMO
OBJECTIVE: Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with reduced bone mineral density (BMD) in persons with HIV (PWH). BMD provides information only about bone mineral quantity. Trabecular bone score (TBS) is a noninvasive tool that estimates bone microarchitecture. The aim of this study is to measure BMD and TBS of Chinese PWH after one-year ART. METHODS: We designed a retrospective study of adult Chinese PWH. Patients with a dual-energy X-ray absorptiometry (DXA) scan prior to ART initiation, and again 48 weeks later were included. Information regarding demographic and clinical history, HIV treatment history, BMD and TBS were collected. We analyzed differences in BMD and TBS over 48 weeks and associations between key risk factors and changes in BMD and TBS. RESULTS: Our study included 233 âPWH (mean age â= â36.6 â± â11.1 years). Before ART initiation, 19.3% of PWH had normal BMD but abnormal TBS. Both BMD and TBS decreased after one-year ART. TDF and LPV/r-containing regimens were associated with greater declines in BMD at different site. Traditional risk factors such as old age, low BMI and female sex were associated with lower baseline TBS. Greater change in TBS over one year was associated with lower BMI and lower baseline CD4+ cell count, but unlike BMD measures, it was not correlated with treatment with TDF and LPV/r in our study population. CONCLUSIONS: We present the first longitudinal analysis of change in TBS over 48 weeks compared with BMD among Asian PWH receiving ART. Before ART initiation, approximately 20% of PWH with impaired bone microarchitecture would not have been identified if DXA were used alone to assess for bone damage. Both BMD and TBS decreased after one-year ART. Change in TBS was not associated with different antiretroviral agents. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The trabecular microarchitecture measured indirectly by TBS may provide clinicians additional information about bone damage in PWH.
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Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.
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COVID-19/patologia , Pulmão/virologia , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Autopsia , COVID-19/virologia , China , Estudos de Coortes , Estado Terminal , Feminino , Fibrose , Hospitalização , Humanos , Rim/patologia , Rim/virologia , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/virologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , RNA Viral/metabolismo , SARS-CoV-2/genética , Baço/patologia , Baço/virologia , Traqueia/patologia , Traqueia/virologiaRESUMO
BACKGROUND: A more time saving, convenient, reproducible, and scalable method is needed to assess total HIV-1 DNA levels. METHODS: Frozen whole blood and peripheral blood mononuclear cell (PBMC) samples both 200 µl at the same point were used to detect total HIV-1 DNA. Automatic extraction of total HIV-1 DNA was used to ensure the consistency of sample extraction efficiency. The detection reagent was HIV-1 DNA quantitative detection kit and real-time quantitative PCR was utilized. RESULTS: Of the 44 included patients, 42 were male and 2 were female, with a median age of 33 years. Thirty-three cases were collected after receiving antiviral treatment, with a median duration of treatment of 3 months, and the other 11 cases were collected before antiviral treatment. The median viral load was 1.83 log10 copies/mL, the median CD4 and CD8 count were 94 and 680 cells/µL, and the median CD4/CD8 ratio was 0.18. The results of the two samples were 3.02 ± 0.39 log10 copies/106 PBMCs in PBMC samples and 3.05 ± 0.40 log10 copies/106 PBMCs in whole blood samples. The detection results of the two methods were highly correlated and consistent by using paired t test (P = 0.370), pearson correlation (r = 0.887, P < 0.0001) and intra-group correlation coefficient (ICC = 0.887, P < 0.0001) and bland-altman [4.55% points were outside the 95% limits of agreement (- 0.340 ~ 0.390)]. CONCLUSIONS: The results of the whole blood sample test for total HIV-1 DNA are consistent with those of PBMC samples. In a clinical setting it is recommended to use whole blood samples directly for the evaluation of the HIV reservoir.
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DNA Viral/sangue , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , HIV-1/genética , Leucócitos Mononucleares/virologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Relação CD4-CD8 , DNA Viral/análise , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: It is not completely clear whether a very high pre-therapy viral load (≥ 500 000 copies/ml) can impair the virological response. The aim of this study was to examine the influence of very high baseline HIV-RNA levels on long-term virological responses under one type of regimen. METHODS: A retrospective study was performed based on data from two multicenter cohorts in China from January to November 2009, and from May 2013 to December 2015. Untreated HIV infected adults between 18 and 65 years old were recruited before receiving non-nucleoside reverse transcriptase inhibitor-based regimen. All patients had baseline HIV-RNA levels over 500 copies/ml, good adherence, and were followed for at least 24 weeks. Virological suppression was defined as the first HIV-RNA < 50 copies/ml. Virological failure was defined as any of incomplete viral suppression (HIV-RNA ≥ 200 copies/ml without virological suppression within 24 weeks of treatment) and viral rebound (confirmed HIV-RNA level ≥ 50 copies/ml after virological suppression). Chi-square test, Kaplan-Meier analysis, Cox proportional hazards model and Logistic regression were used to compare virological response between each pretreated viral load stratum. RESULTS: A total of 758 treatment-naïve HIV patients in China were enlisted. Median follow-up time (IQR) was 144 (108-276) weeks. By week 48, rates of virological suppression in three groups (< 100 000, 100 000-500 000 and ≥ 500 000 copies/ml) were 94.1, 85.0, and 63.8%, respectively (P < 0.001). Very high baseline HIV viremia over 500 000 copies/ml were found to be associated with delayed virological suppression (≥ 500 000 vs < 100 000, adjusted relative hazard = 0.455, 95% CI: 0.32-0.65; P < 0.001) as well as incomplete viral suppression (≥ 500 000 vs < 100 000, adjusted odds ratio [aOR] = 6.084, 95% CI: 2.761-13.407; P < 0.001) and viral rebound (≥ 50 000 vs < 100 000, aOR = 3.671, 95% CI: 1.009-13.355, P = 0.048). CONCLUSIONS: Very high levels of pre-treatment HIV-RNA were related with delayed efficacy of NNRTI-based ART and increased risk of treatment failure. More potent initial regimens should be considered for those with this clinical character.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Viremia/tratamento farmacológico , Adulto , Idoso , China , Estudos de Coortes , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , DNA Polimerase Dirigida por RNA/uso terapêutico , Estudos Retrospectivos , Carga Viral , Viremia/sangue , Viremia/virologiaRESUMO
The objective of this study was to predict the value of lymphocyte subsets in cancer progression. Peripheral blood was obtained from 327 untreated patients with cancer and 158 healthy volunteers. Levels of lymphocyte subsets were determined by flow cytometry. There were decreased levels of natural killer (NK) cells, CD8+ T cells, and naïve CD4+ /CD4+ T cells in untreated patients with cancer compared to those in healthy controls. Inversely, there were elevated levels of the following T-cell percentages in cancer patients compared to those in healthy controls: memory CD4+ /CD4+ , CD8+ T cells, HLA-DR/CD8+ , CD8+ CD38+ /CD8+ , and CD4+ /CD8+ . In addition, there are a decreasing trend in terms of CD4+ T-cell counts and an increase CD8+ HLA-DR/CD8+ T-cell and CD8+ CD38+ /CD8+ T-cell percentages in the advanced stage. An increasing trend with advanced tumor stage and the percentages of CD8+ HLA-DR/CD8+ T cells and CD8+ CD38+ /CD8+ T cells was shown in this study. There are a negative correlation for CD4+ T-cell counts and positive correlation for percentages of CD8+ HLA-DR/CD8+ T cell and CD8+ CD38+ /CD8+ T cells with the lymph node metastasis. In the presence of distant metastatic spread, we observed higher NK-cell counts, CD8+ HLA-DR/CD8+ T-cell percentages, CD8+ CD38+ /CD8+ T-cell percentages, as well as lower CD4+ T-cell counts than those in the absence of distant metastases spread. Abnormal levels of NK cell, CD8+ T cells, memory CD4+ /CD4+ , naïve CD4+ / CD4+ , CD8+ HLA-DR/CD8+ , CD8+ CD38+ /CD8+ , and CD4+ /CD8+ can be a potential blood biomarkers of cancer development. CD4+ T-cell counts and percentages of CD8+ HLA-DR/ CD8+ and CD8+ CD38+ / CD8+ can predict the cancer progression.
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Biomarcadores Tumorais/metabolismo , Contagem de Linfócitos/métodos , Linfócitos/metabolismo , Neoplasias/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral , Adulto JovemAssuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Doenças do Sistema Nervoso Central/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Toxoplasma/patogenicidade , Resultado do TratamentoRESUMO
Objective To explore whether baseline body composition and other clinical factors are associated with incomplete immune response after highly active antiretroviral therapy(HAART)in Chinese men with human immunodeficiency virus(HIV)or acquired immunodeficiency syndrome(AIDS).Methods A retrospective study was conducted among HIV/AIDS male patients who achieved viral suppression(maintained HIV-1 RNA levels<400 copies/ml)after a year of HAART between 2007 and 2015.Clinical,immunological,and virological data were collected from patients' files,including weight,height,and whole body composition measured within one month prior to staring HAART.Body mass index(BMI),lean mass index(LMI),fat mass index(FMI),and body bone mineral content/height were adjusted by height.According to whether the patients experienced incomplete immune responses(CD4 cell count<350 cells/µl)after a year of HAART,the patients were divided into two groups:the complete immune response(CD4 cell count≥350 cells/µl)and the incomplete immune response(CD4 cell count<350 cells/µl),respectively.Student's t test,chi-square test,and Wilcoxon rank test were used to assess differences between these two groups.Multiple Logistic regression analysis was used to assess factors associated with an incomplete immune response in patients with sustained viral suppression.Results Totally 84 HIV/AIDS male patients with viral suppression were included in this study.There were statistical differences between these two groups in terms of age(Z=-2.479,P=0.013),baseline BMI(t=2.030,P=0.045),LMI(t=2.200,P=0.029),and CD4 cell count(Z=6.416,P=0.000).However,there was no statistical differences in viral load,FMI,body bone mineral content/height,HAART duration,and HAART regimen(all P>0.05).BMI[OR=0.742,95% confidence interval(CI)=0.554-0.993,P=0.044],LMI(OR=0.459,95% CI=0.249-0.844,P=0.012),HAART duration(OR=10.161,95% CI=1.110-93.052,P=0.040),baseline CD4 cell count(OR=80.051,95% CI=8.396-762.563,P=0.000)were significantly associated with incomplete immune response.Age(OR=1.497,95% CI=0.213-10.505,P=0.685),viral load(OR=0.333,95% CI=0.071-1.572,P=0.164),FMI(OR=0.797,95% CI=0.546-1.164,P=0.240),body bone mineral content/height(OR=1.145,95% CI=0.037-35.676,P=0.938)and HAART regimen(OR=0.430,95% CI=0.159-1.159,P=0.095)were not associated with incomplete immune response.Conclusions Baseline CD4 cell count and HAART duration may affect immune response.Patients with higher baseline BMI or higher LMI may be less likely to develop incomplete immune response.Baseline FMI and body bone mineral content/height ratio are not associated with incomplete immune response.
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Terapia Antirretroviral de Alta Atividade , Composição Corporal , Infecções por HIV/tratamento farmacológico , Contagem de Linfócito CD4 , Infecções por HIV/imunologia , Humanos , Masculino , Estudos Retrospectivos , Carga ViralRESUMO
Delayed diagnosis of HIV infection is associated with advanced immunosuppression and increased risk of onward transmission. Little data exists regarding factors associated with diagnostic delays among patients presenting with advanced HIV disease in China. Medical records of patients with HIV/AIDS hospitalized at a 2000-bed tertiary hospital in Beijing, China between 1997 and 2012 were retrospectively reviewed. Demographic and clinical data of patients newly diagnosed with HIV at the hospital were abstracted. Patient characteristics, disease parameters, and the time interval between the first medical visit and the visit leading to HIV diagnosis were compared among three periods: 1997-2002, 2003-2008 and 2009-2012. Chi-square, Kruskal-Wallis and logistic regression analyses were used as appropriate. A quarter of patients (72/279) were newly diagnosed with HIV at the hospital, consisting of 11, 29 and 32 patients in 1997-2002, 2003-2008 and 2009-2012 respectively. The median time delay between the first medical visit and the visit leading to HIV diagnosis decreased over time from 91 days among patients diagnosed before 2002, to 75 days between 2003 to 2008, and 39 days after 2009 (p = 0.036). However, the median CD4+T cell count at diagnosis was 26 cells/µL [interquartile range 3-132 cells/µL] in 1997-2002, and remained unchanged across time intervals. Forty-one (57%) patients had AIDS-defining conditions and Pneumocystis jiroveci pneumonia was the most common opportunistic infection (31 cases). These results reveal persistent missed opportunities for timely HIV testing among patients with advanced disease. Strategies for promoting early HIV testing in healthcare settings are needed in China.
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Síndrome da Imunodeficiência Adquirida/diagnóstico , Diagnóstico Tardio/estatística & dados numéricos , Programas de Rastreamento/métodos , Centros de Atenção Terciária/estatística & dados numéricos , Infecções Oportunistas Relacionadas com a AIDS/complicações , Adulto , Contagem de Linfócito CD4 , China , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Elucidation of mechanisms underlying the establishment, maintenance of and reactivation from HIV-1 latency is essential for the development of therapeutic strategies aimed at eliminating HIV-1 reservoirs. Microbial translocation, as a consequence of HIV-1-induced deterioration of host immune system, is known to result in a systemic immune activation and transient outbursts of HIV-1 viremia in chronic HIV-1 infection. How these microbes cause the robust HIV-1 reactivation remains elusive. Dendritic cells (DCs) have previously been shown to reactivate HIV-1 from latency; however, the precise role of DCs in reactivating HIV-1 from latently infected T-cell remains obscure. In this study, by using HIV-1 latently infected Jurkat T cells, we demonstrated that AIDS-associated pathogens as represented by Mycobacterium bovis (M. bovis) Bacillus Calmette-Guérin (BCG) and bacterial component lipopolysaccharide (LPS) were unable to directly reactivate HIV-1 from Jurkat T cells; instead, they mature DCs to secrete TNF-α to accomplish this goal. Moreover, we found that HIV-1 latently infected Jurkat T cells could also mature DCs and enhance their TNF-α production during co-culture in a CD40-CD40L-signaling-dependent manner. This in turn led to viral reactivation from Jurkat T cells. Our results reveal how DCs help AIDS-associated pathogens to trigger HIV-1 reactivation from latency.
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Síndrome da Imunodeficiência Adquirida/metabolismo , Células Dendríticas/imunologia , HIV-1/fisiologia , Células Jurkat/virologia , Fator de Necrose Tumoral alfa/farmacologia , Latência Viral , Síndrome da Imunodeficiência Adquirida/genética , Síndrome da Imunodeficiência Adquirida/virologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Técnicas de Cocultura , Células Dendríticas/citologia , HIV-1/genética , Humanos , Células Jurkat/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Ativação ViralRESUMO
OBJECTIVES: This study aimed to examine the long-term efficacy, remission and survival of patients with severe systemic lupus erythematosus (SLE) after the combination treatment with high-dose immunosuppressive therapy (HDIT) and autologous peripheral blood stem cell transplantation (APBSCT). METHODS: Chinese patients with severe SLE receiving combination therapy with HDIT and APBSCT in Peking Union Medical College Hospital were enrolled from July 1999 to October 2005. Disease activity, treatment, and adverse effects of these patients were evaluated. The 10-year overall survival and 10-year remission survival were also analysed. RESULTS: Among the 27 patients, one patient failed to collect enough CD34+ cells and data was missing for two patients. In the end, 24 patients were included in the final analysis. After APBSCT, one patient died, two patients achieved partial remission and 21 (87.5%) achieved remission at 6 months. The median follow-up duration of the 23 patients was 120 months. Fourteen patients had completed a ten-year follow-up. The median proteinuria level of the 14 patients with LN with ten years of follow-up significantly decreased from 4.00 g/24 hours at pre-treatment to 0.00g/24 hours at year 5 and 0.00 g/24 hours at year 10 (both p=0.001). The 10-year overall survival rate and 10-year remission survival rate were both 86.0% (95% CI: 71.1-100.9%). After a median follow-up for 120 months, 16 patients (66.7%) remained in remission, 4 patients were lost to follow-up, 2 patients died and 1 patient remained active. CONCLUSIONS: The combination of HDIT and APBSCT may be an option to improve the survival of severe lupus patients.
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Imunossupressores/administração & dosagem , Nefrite Lúpica/terapia , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , China , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Estimativa de Kaplan-Meier , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Recidiva , Indução de Remissão , Índice de Gravidade de Doença , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance. DATA SOURCES: Literatures related to the size of HIV DNA was collected from PubMed published from 1999 to June 2016. STUDY SELECTION: All relevant articles on the HIV DNA and reservoir were collected and reviewed, with no limitation of study design. RESULTS: The composition and development of the HIV-1 DNA reservoir in either treated or untreated patients is determined by integrated mechanism comprising viral characteristics, immune system, and treatment strategies. The HIV DNA reservoir is a combination of latency and activity. The residual viremia from the stochastic activation of the reservoir acts as the fuse, continuing to stimulate the immune system to maintain the activated microenvironment for the rebound of competent virus once treatment with antiretroviral therapy is discontinued. CONCLUSION: The size of the HIV-1 DNA pool and its composition has great significance in clinical treatment and disease progression.
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Fármacos Anti-HIV/uso terapêutico , DNA Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/patogenicidade , Feminino , Infecções por HIV/genética , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Carga Viral/efeitos dos fármacos , Carga Viral/genética , Viremia/tratamento farmacológico , Viremia/genéticaRESUMO
The incidence of human immunodeficiency virus (HIV) infection has gradually increased in recent years.HIV mainly destroys the body's immune system,leading to decreased body resistance and thus the development of a variety of opportunistic infections and neoplastic diseases,especially in the digestive system. However,the clinical manifestations,laboratory findings,and physical examination results of these conditions are not specific. Imaging examinations can determine the presence of infection and tumor lesions and the disease scope;furthermore,they are useful tools for biopsy and follow-up evaluation. A better knowledge of the radiological findings of these diseases can enable radiologists to provide more information to patients and clinicians. This article summarize the imaging findings of common opportunistic infections and malignant tumors in acquired immunodeficiency syndrome patients.
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Infecções Oportunistas , Síndrome da Imunodeficiência Adquirida , Humanos , NeoplasiasRESUMO
INTRODUCTION: Although HIV antibody tests have been widely accepted in clinical diagnosis of HIV infection, they may not be sufficient to diagnose all subjects with HIV infection. Except negative result of antibody test in the well-known" acute window phase", in rare cases, patients do not develop HIV antibodies despite demonstrable infection. Primary pulmonary Kaposi sarcoma (KS) without mucocutaneous involvement accounts for only 0-15% of all AIDS-related KS. KS is rare among Chinese subjects, especially in persons of Han descent. METHODS: A case of seronegative AIDS with primary pulmonary Kaposi sarcoma (KS) was reported. It's a 46-year-old Chinese man presented with sore throat, hemoptysis, fever, dyspnea and multiple lung nodules. The lung lesions grew over a 5-month period so as the symptoms worsened. The possibility of AIDS was discounted by his physicians because of the repeatedly negative HIV antibodies tests despite the ELISA tests or Western blot tests. Histopathologic diagnosis of fine needle lung biopsy in local hospital was undetermined. After admission, HIV infection was eventually confirmed by plasma HIV RNA testing. Histopathologic diagnosis of Lung Kaposi sarcoma was made through repeated fine needle aspiration biopsy as well as the review of former one. Multiple antibiotics and chemotherapy were administrated with no clinical effect due to advanced stage and the patient passed away soon after diagnosis. RESULTS: This is the first case of seronegative HIV-1 infection with presentation of primary pulmonary KS. CONCLUSION: This case underscores the importance of plasma RNA test in conjunction with HIV antibody test for some rare patients with HIV infection who present with severe immunodeficiency and opportunistic infections or malignancy.
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Infecções Oportunistas Relacionadas com a AIDS/complicações , Síndrome da Imunodeficiência Adquirida/complicações , Infecções por HIV/complicações , Soronegatividade para HIV/imunologia , Neoplasias Pulmonares/patologia , Sarcoma de Kaposi/patologia , Síndrome da Imunodeficiência Adquirida/diagnóstico , Evolução Fatal , HIV/genética , HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/genética , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Among HIV-infected patients initiating antiretroviral therapy (ART), early changes in CD4+ T-cell subsets are well described. However, HIV-infected late presenters initiating treatment present with a suboptimal CD4+ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events. Therefore, factors associated with CD4+ T-cell reconstitution need to be determined in this population, which will allow designing effective immunotherapeutic strategies. METHODS: Thirty-one adult patients with baseline CD4+ T-cell count <350 cells/mm3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing, China, from October 2002 to September 2013. Changes in T-cell subsets and associated determinants were measured. RESULTS: Median baseline CD4+ T-cell count was 70 cells/mm3. We found a biphasic reconstitution of T-cell subsets and immune activation: a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years. Baseline CD4+ T-cell count >200 cells/mm3 in comparison to CD4+ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution (77.8% vs. 27.3% respectively; P = 0.017) and normalized CD4/CD8 ratio. We showed that the baseline percentage of naive CD4+ T-cell was a predictive marker for complete immune reconstitution (area under receiver operating characteristic curve 0.907), and 12.4% as cutoff value had a sensitivity of 84.6% and a specificity of 88.2%. CONCLUSIONS: Baseline naive CD4+ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy. Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.
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Linfócitos T CD4-Positivos/metabolismo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Relação CD4-CD8 , Feminino , Infecções por HIV/metabolismo , HIV-1/efeitos dos fármacos , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Masculino , Estudos Prospectivos , Subpopulações de Linfócitos T/imunologiaRESUMO
Approximately 70% of HIV-1 infected patients acquire ocular opportunistic infections and manifest eye disorders during the course of their illness. The mechanisms by which pathogens invade the ocular site, however, are unclear. Under normal circumstances, vascular endothelium and retinal pigment epithelium (RPE), which possess a well developed tight junction complex, form the blood-retinal barrier (BRB) to prevent pathogen invasion. We hypothesize that disruption of the BRB allows pathogen entry into ocular sites. The hypothesis was tested using in vitro models. We discovered that human RPE cells could bind to either HIV-1 gp120 glycoproteins or HIV-1 viral particles. Furthermore, the binding was mediated by dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) expressed on RPE cells. Upon gp120 binding to DC-SIGN, cellular NF-κB signaling was triggered, leading to the induction of matrix metalloproteinases, which subsequently degraded tight junction proteins and disrupted the BRB integrity. DC-SIGN knockdown or prior blocking with a specific antibody abolished gp120-induced matrix metalloproteinase expression and reduced the degradation of tight junction proteins. This study elucidates a novel mechanism by which HIV, type 1 invades ocular tissues and provides additional insights into the translocation or invasion process of ocular complication-associated pathogens.
Assuntos
Barreira Hematorretiniana/metabolismo , Moléculas de Adesão Celular/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , Infecções por HIV/metabolismo , HIV-1/metabolismo , Lectinas Tipo C/metabolismo , Receptores de Superfície Celular/metabolismo , Junções Íntimas/metabolismo , Barreira Hematorretiniana/virologia , Moléculas de Adesão Celular/genética , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/genética , Humanos , Lectinas Tipo C/genética , Permeabilidade , Ligação Proteica , Receptores de Superfície Celular/genética , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/genética , Junções Íntimas/virologiaRESUMO
BACKGROUND: The prevalence of thrombocytopenia among Chinese antiretroviral therapy (ART)-naïve HIV-infected adults has not been well-described. The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-naïve HIV-infected adults. METHODS: We performed a cross-sectional study of Chinese adult ART-naïve HIV-infected patients from September 2005 through August 2014. Socio-demographic variables and laboratory results including platelets, CD4+ cell count, and viral load were obtained from medical records. Factors and outcomes associated with thrombocytopenia were assessed using logistic regression. RESULTS: A total of 1730 adult ART-naïve HIV-infected patients was included. The mean age was 38 years. The prevalence of thrombocytopenia was 4.5%. There were significant differences in the prevalence of thrombocytopenia between patients <30 years of age (2.8%) and 30-39 years (4.0%) compared with patients greater than 50 years (7.0%) (P = 0.006 and P = 0.044, respectively). The prevalence of thrombocytopenia was also significantly different between patients with CD4+ counts of 200-349 cells/mm 3 (3.3%) and >350 cells/mm 3 (2.8%) compared with patients with CD4+ counts of 50-199 cells/mm 3 (7.1%) (P = 0.002 and P = 0.005, respectively). The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab) seropositivity (10.2% for HCV-Ab positive vs. 3.9% for HCV-Ab negative, P = 0.001). We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection: Blood transmission (10.7%) versus men who have sex with men (3.9%) (P = 0.002) and versus heterosexual transmission (3.9%) (P = 0.001). In binary logistic regression analyses, age ≥ 50 years, HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm 3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]: 1.167, 5.281, P = 0.018), 2.091 (95% CI: 1.078, 4.055, P = 0.029) and 2.259 (95% CI: 1.028, 4.962, P = 0.042), respectively. CONCLUSIONS: Thrombocytopenia is not common among adult ART-naïve HIV-infected patients in China. Older age (age over 50 years), HCV-Ab positivity and lower CD4+ cell count are associated with an increased risk of thrombocytopenia. Therefore, early diagnosis and treatment of thrombocytopenia in these patients are necessary.