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1.
目的了解经性传播途径高暴露HIV-1持续血清阴性者淋巴细胞亚群表达及其免疫活化状态,探讨经性途径高暴露HIV-1不易感的免疫基础。方法收集37例经性传播途径高暴露HIV—1持续血清阴性者(简称HEPS人群)、65例经性传播途径感染HIV-1者(简称HIV+人群)、128例健康对照者(简称HC人群)的抗凝全血,用流式细胞仪检测。结果HEPS人群和HC人群的CD4绝对数、CD4/CD8比值高于HIV+人群(P〈0.001),而该两类人群的CD8^+绝对数则低于HIV+人群(P〈0.001);HEPS人群和HC人群的CD38^+/CD4^+、HLA-DR^+ CD38^+/CD4^+百分比低于HIV+人群(P〈0.001),同时HEPS人群的HLA—DR—CD38^+/CD4^+百分比低于HC人群(P〈0.05);HEPS人群的HLA—DR^+/CD4^+百分比低于HIV+人群和HC人群(P〈0.001)。结论HEPS人群对HIV-1的不易感性可能与其T淋巴细胞表面标志活化抗原表达水平处于较低水平状态有关。  相似文献   

2.
Thisyakorn U  Pancharoen C  Wilde H 《Vaccine》2001,19(11-12):1534-1537
BACKGROUND: One-third of Thai children experience a dog bite by the time they are 15 years old, and HIV-1 infection in children is also not uncommon. Previous study has shown that rabies vaccination of HIV-1-infected children may not result in a satisfactory antibody response when CD4+ T cells are less than 15%. The objective of this prospective clinical study is to evaluate the immunologic response and effect on viral load after rabies vaccination in HIV-infected children. METHODS: Thirteen HIV-1-infected children were vaccinated with the intramuscular rabies pre-exposure regimen using human diploid cell rabies vaccine (HDCV) on days 0, 7 and 28. CD4+ and CD8+ lymphocyte counts were performed on days 0, 7 and 28. Plasma viral loads were determined on days 0, 7, 14, 60, 90, 180 and 360. RESULTS: There were no significant change in serial measurements of CD4+/CD8+ lymphocytes during a period of 1 month and in plasma viral load during 1 year. There was no associated clinical deterioration or any adverse reactions attributable to vaccine. CONCLUSIONS: Rabies vaccination in HIV-1-infected children appears to be safe but did not significantly change the levels of plasma HIV RNA, CD4+ and CD8+ cell counts.  相似文献   

3.
目的 研究HIV-1感染者CD8+T细胞受体(TCR)基因的多样性变化特征及其与病毒载量的相关性.方法 应用抗CD8单克隆抗体从9份HIV-1感染者和7份HIV-1阴性对照样本外周血单个核细胞中分离CD8+T细胞,提取总RNA,然后采用一步(one step)及巢式(nested)多聚酶链式反应(PCR)的方法对22个T细胞受体Vβ基因家族的瓦补决定区3(CDR3)进行扩增,利用ABI-3700测序仪对扩增的PCR产物进行扣描,定量分析HIV-1感染者TCR CDR3区多样性变化特征及其与病毒载量的相关性.结果 HIV-1感染者和正常人相比较其CD8+T细胞的TCR基因多样性明显减少,部分TCR Vβ基因家族CDR3区的高斯分布破坏;TCR的紊乱与病毒载量呈正相关(r=0.771,P<0.05);HIV-1感染引起患者TCR多样性的改变不仅表现在不同Vβ基因家族上,而且也表现在CDR3长度上,其中感染者VB2、Vβ4、Vβ5、Vβ17、Vβ20、Vβ21、Vβ23及Vβ24基因家族的变化与正常人存在统计学差异.结论 HIV-1感染能引起CD8+T细胞TCR基因多样性的减少及高斯分布的破坏,TCR CDR3区的紊乱与病毒载量呈正相关.  相似文献   

4.
Liu J  Yu Q  Stone GW  Yue FY  Ngai N  Jones RB  Kornbluth RS  Ostrowski MA 《Vaccine》2008,26(32):4062-4072
Human immunodeficiency virus type 1 (HIV-1) canarypox vaccines are safe but poorly immunogenic. CD40 ligand (CD40L), a member of the tumor necrosis factor superfamily (TNFSF), is a pivotal costimulatory molecule for immune responses. To explore whether CD40L can be used as an adjuvant for HIV-1 canarypox vaccine, we constructed recombinant canarypox viruses expressing CD40L. Co-immunization of mice with CD40L expressing canarypox and the canarypox vaccine expressing HIV-1 proteins, vCP1452, augmented HIV-1 specific cytotoxic T lymphocyte (CTL) responses in terms of frequency, polyfunctionality and interleukin (IL)-7 receptor alpha chain (IL-7Ralpha, CD127) expression. In addition, CD40L expressed from canarypox virus could significantly augment CD4+ T cell responses against HIV-1 in mice. CD40L expressed from canarypox virus matured human monocyte-derived dendritic cells (MDDCs) in a tumor necrosis factor-alpha (TNF-alpha) independent manner, which underwent less apoptosis, and could expand ex vivo Epstein-Barr virus (EBV)-specific CTL responses from healthy human individuals and ex vivo HIV-1-specific CTL responses from HIV-1-infected individuals in the presence or absence of CD4+ T cells. Taken together, our results suggest that CD40L incorporation into poxvirus vectors could be used as a strategy to enhance their immunogenicity.  相似文献   

5.
OBJECTIVE: To evaluate functional potential and phenotypic markers in HIV-1-infected patients immunized with HIV-1 rgp160. METHODS: We assessed changes in T-cell phenotype and immune function in 12 HIV-1-infected individuals that were part of a therapeutic vaccine study from 1992 to 1995 [Sandstrom E, Wahren B. Therapeutic immunisation with recombinant gp160 in HIV-1 infection: a randomised double-blind placebo-controlled trial. Nordic VAC-04 Study Group. Lancet 1999;353(9166):1735-42]. The patients received 160mug HIV-1 rgp160 or placebo i.m. at baseline (day 0), and months 1, 2, 3, 4, 6, and thereafter every 3 months. Frozen peripheral blood mononuclear cells (PBMC) were retrieved from time points 0, 9, 12 and 24 months for phenotypic analysis utilizing flow cytometry. RESULTS: Up-regulation of immune activation markers HLA-DR and CD38 was observed at baseline and throughout the monitoring period on both CD4(+) and CD8(+) T cells in all patients, reflecting immune activation due to persistent high viral load. Further enhanced expression of activation markers was observed over time in the vaccine group, but not the placebo group. We also observed a consistent long-term increase of the CD4(+) central memory population (CD3(+)CD4(+)CD45RA(-)CCR7(+)) in the vaccinated group. CONCLUSIONS: Administration of eight doses of rgp160 in a year appeared to partially reverse some of the defects exerted by HIV-1 on the immune system. A combination of vaccination with effective antiretroviral therapy (ART) may thus represent an immunotherapeutic intervention for treatment of chronic HIV-1 infection. The improvement of a HIV-1-specific central memory population and HIV-1 antigen-specific CD4(+) lymphoproliferative responses may have contributed to the short-term improved survival reported in the vaccinated group.  相似文献   

6.
We studied HIV-positive and -negative subjects for T-cell reactivity to rCD4, and found that 80% of 25 tested HIV-infected patients and 25% of controls manifested T-cell proliferation responses to rCD4. We mapped the major CD4 immunogenic epitopes among the CD4+ responders of both groups by testing T-cell proliferation responses to 31 synthetic overlapping peptides from the human CD4 molecule. Such responses to p1, p4, p14, p21, p28 and p29 were significantly higher in the eight infected patients and, with the exception of p14, these peptides differed from those found in three HIV-negative controls (p11, p14 and p27). Peptides p1, p28 and p29 are major immunogenic epitopes. Our findings suggest: (1) that HIV infection is associated with T-cell reactivity to CD4; and (2) that the use of synthetic CD4 peptides to replace the complete CD4 molecule may therefore lead to a cost-effective T-cell vaccination for HIV-positive patients exhibiting anti-CD4 autoimmunity, as well as to the development of complimentary TCR peptides for future peptide vaccinations.  相似文献   

7.
Tetanus and diphtheria (Td) antibodies were studied in HIV-1-infected women during puerperium. HIV group (n=61) was compared with Control group (n=101). Twenty-one women from HIV and 13 from Control group who had antibody levels lower than 0.1 IU/mL received a booster with Td vaccine. Antibodies were assessed by double antigen ELISA. Mean tetanus and diphtheria antibody levels from HIV group were lower than those from Control group. Multiple linear regression analysis showed that tetanus and diphtheria antibody levels were decreased by HIV-1-infection, and that was independent of the reduction due to the time interval between last booster and antibody assessment. After a booster dose, both groups had an increase in mean tetanus and diphtheria antibody levels, but in Control group the levels were higher than in HIV group.  相似文献   

8.
Veiga AP  Casseb J  Duarte AJ 《Vaccine》2006,24(49-50):7124-7128
HIV disease leads to defects in cell-mediated immunity, impairing the immune response to new and recall antigens. We studied 55 HIV 1-infected patients who received of recombinant DNA hepatitis B vaccine and 20 controls. The overall hepatitis B virus (HBV) seroconversion rate was 59%. The median CD4+ T cell count among responders was 452 cell/mm(3), higher than non-responders (359 cells/mm(3)). The HIV plasmaviral loads were higher in non-responders. We concluded that total T CD4 cell count, memory T CD4+ cells and lower plasma viral load among HIV-1-infected subjects treated with HAART could be used to predict the immune response to vaccination with hepatitis B vaccine. Thus, considering cost benefits, HVB vaccination should be preferentially provided to HIV-infected patients with T CD4 cells count over 450 cells/mm(3), preferentially whose under HIV replication controlled.  相似文献   

9.
We assessed the impact of HIV-1 on malaria in the sub-Saharan African population. Relative risks for malaria in HIV-infected persons, derived from literature review, were applied to the HIV-infected population in each country, by age group, stratum of CD4 cell count, and urban versus rural residence. Distributions of CD4 counts among HIV-infected persons were modeled assuming a linear decline in CD4 after seroconversion. Averaged across 41 countries, the impact of HIV-1 was limited (although quantitatively uncertain) because of the different geographic distributions and contrasting age patterns of the 2 diseases. However, in Botswana, Zimbabwe, Swaziland, South Africa, and Namibia, the incidence of clinical malaria increased by < or =28% (95% confidence interval [CI] 14%-47%) and death increased by < or =114% (95% CI 37%-188%). These effects were due to high HIV-1 prevalence in rural areas and the locally unstable nature of malaria transmission that results in a high proportion of adult cases.  相似文献   

10.
The aim of this study was determine the prevalence of Mycoplasma hominis, M. genitalium, M. fermentans, M. pirum, M. penetrans and Ureaplasma urealyticum in HIV-infected patients. Culture and PCR were used to detect six species of Mycoplasma in first-void urine of HIV-1 infected men. A total of 497 HIV/AIDS patients (age range 5-75 years, mean 37 years) were screened in the study. All presented positive for at least one kind of mycoplasma, especially U. urealyticum and M. hominis. Six mycoplasmas were significant in the homosexual contact and heterosexual contact groups. The distribution of M. hominis, M. penetrans, and M. pirum were significantly different in this four-transmission category. CD4+ cell count levels were lower in the AIDS-associated Mycoplasma-positive group than in the Mycoplasma-negative group (P<0.01). This study indicates that U. urealyticum, M. hominis and M. fermentans are prevalent in HIV-1-infected male patients. This may be an indication of whether mycoplasmas are co-factors in the progression of HIV disease.  相似文献   

11.
12.
HIV genetic variability, phylogenetic relationships, and transmission dynamics were analyzed in 26 HIV-infected patients from Lebanon. Twenty-five specimens were identified as HIV-1 and one as HIV-2 subtype B. The 25 strains were classified into six env-C2-V3 HIV-1 subtypes: B (n = 10), A (n = 11), C (n = 1), D (n = 1), G (n = 1), and unclassifiable. Potential recombinants combining parts of viral regions from different subtypes Aenv/Dpol/Agag, Genv/Apol, and the unclassifiable-subtype(env)/unclassifiable-subtype(pol)/Agag were found in three patients. Epidemiologic analysis of travel histories and behavioral risks indicated that HIV-1 and HIV-2 subtypes reflected HIV strains prevalent in countries visited by patients or their sex partners. Spread of complex HIV-subtype distribution patterns to regions where HIV is not endemic may be more common than previously thought. Blood screening for both HIV-1 and HIV-2 in Lebanon is recommended to protect the blood supply. HIV subtype data provide information for vaccine development.  相似文献   

13.
目的 了解病毒学抑制的HIV - 1感染者CD4+ T淋巴细胞免疫衰老状态,探索主成分分析法能否用于评价HIV - 1患者的免疫衰老。方法 选择抗逆转录疗法治疗半年以上成年病毒学抑制HIV - 1感染者,根据CD4+T淋巴细胞计数结果分为CD4无缺陷组(≥500个/μl)和缺陷组(<500个/μl),每组65人,另选择22名未暴露且HIV - 1抗体检测阴性者作为对照组,采用流式细胞仪检测其CD4+T淋巴细胞(CD45RA+CD27+)、活化CD4+T淋巴细胞(HLA - DR+CD38+)和复制性衰老CD4+T淋巴细胞(CD57+CD28-)水平,运用主成分分析对三种细胞进行综合分析。结果 缺陷组(27.64%)和无缺陷组(32.04%)的初始CD4+T淋巴细胞较对照组(51.27%)有明显下降(F = 24.35,P<0.001),活化CD4+T淋巴细胞(14.26%,13.03%)较对照组(2.35%)有明显上升(F = 19.75,P<0.001);缺陷组(12.64%)的复制性衰老CD4+T淋巴细胞较无缺陷组(7.36%)和对照组(3.58%)有明显升高(F = 6.68,P = 0.002),而无缺陷组和对照组之间无统计学差异;主成分分析能区分出三组对象CD4+T淋巴细胞免疫衰老的差异程度:缺陷组>无缺陷组>对照组(F = 20.787,P<0.001)。结论 病毒学抑制良好的HIV - 1感染者即使CD4+T细胞数量正常也表现为免疫衰老,CD4+T细胞数量异常的人免疫衰老状态更严重,可运用主成分分析对病毒学抑制的HIV - 1感染者免疫衰老相关细胞进行综合分析。  相似文献   

14.
ObjectivesHIV-infected individuals are at higher risk of non-AIDS diseases associated with procoagulant status. Microparticles are elevated in disorders associated with thrombosis (e.g., cardiovascular diseases). We investigated the association between microparticle levels in untreated and treated HIV-infected subjects, and determined the association with immune status, viral replication, and duration of antiretroviral therapy.Patients and methodsWe included 144 HIV-infected subjects, including 123 on antiretroviral therapy (ART) and 21 before treatment initiation. A control group of 40 HIV-negative healthy adults matched for age and sex was used for comparison of microparticle levels. Treated subjects were divided into five groups depending on the period of antiretroviral exposure. Statistically significant differences were determined by Kruskal–Wallis test and Chi2 test. The relation between microparticles and other parameters was assessed using Spearman's coefficient of correlation.ResultsMicroparticle levels were significantly higher in treated and untreated HIV-infected subjects than in non-HIV-infected controls (P < 0.001). The microparticle level was similar between the groups on treatment (P = 0.913). No association between the microparticle level and CD4+ count, CD4+/CD8+ ratio, number of HIV-1 RNA copies, or duration of exposure to antiretroviral treatment was observed.ConclusionIncreased levels of microparticles may be due to processes independent of viral replication and CD4+ cell count, and microparticle release might persist even during viral suppression by antiretroviral treatment. Elevated microparticle levels might occur in response to other triggers.  相似文献   

15.
OBJECTIVE: Registration of the number of children born to HIV-infected mothers diagnosed prepartum and analysis of the efficacy of the policy for preventing mother-to-child transmission of HIV-1 in the period 1995 to 1999. DESIGN: Prospective. METHOD: On a monthly basis, Dutch paediatricians reported HIV-1 exposed children to the Dutch Paediatric Surveillance Unit. All reports were followed up with standard questionnaires. An additional retrospective study was performed because of incomplete registration. Paediatricians in centres for the care of HIV-infected patients were requested to retrospectively report HIV-exposed children. The standard questionnaires were submitted to these paediatricians. Data were collected during the period 1 January 1995-31 December 1999. RESULTS: The number of children known to be exposed to HIV-1 and for whom the mother was diagnosed prepartum, increased from 5 to 25 per year. The percentage of HIV-1 infected children decreased from 20% (1/5) to 4% (1/25). The number of pregnant HIV-1 infected women using highly active antiretroviral therapy increased during the study period from 0% (0/5) to 72% (18/25). Antiretroviral therapy was administered to 92% (23/25) of HIV-1 exposed children. In total 2% of the children received breastfeeding. CONCLUSION: Despite an increase in the number of children known to be exposed to HIV-1, a decrease in the percentage of HIV-1-infected children was observed. Of the children born in 1999 and known to be exposed to HIV-1, 4% were infected. Measures taken in the Netherlands to prevent mother-to-child transmission of HIV-1 infection are effective.  相似文献   

16.
目的 了解凉山州艾滋病病毒感染者/艾滋病患者(HIV/AIDS)阴性配偶HIV血清阳转率及影响因素。方法 于 2009年1月1日—2019年12月31日,在HIV/AIDS的阴性配偶中进行回顾性队列研究,进行HIV检测及危险行为调查,采用Cox比例风险模型分析HIV感染配偶抗体阳转率的影响因素。结果 共纳入7 989名HIV感染配偶,总观察人时7 291.24人年,随访期间217名HIV感染配偶发生血清阳转,血清阳转率为2.98/100人年。多因素分析显示,文化程度小学以下(aHR = 1.86)、HIV/AIDS患者为女性(aHR = 2.13)、年龄≤35岁(aHR = 1.38)、确证感染时间<1年(aHR = 3.74)、夫妻间性行为频率>4次/月(aHR = 1.37)、病毒载量≥400拷贝/ml(aHR = 1.57)、近一次CD4细胞计数<200个/μl(aHR = 1.81)是HIV感染配偶抗体阳转的危险因素,抗病毒治疗3年以上(aHR = 0.69)是HIV感染配偶抗体阳转的保护因素。结论 凉山州HIV感染配偶抗体阳转率处于较高水平,性行为频次高、文化程度低、年龄≤35岁、HIV/AIDS患者为女性、诊断感染时间<1年、病毒载量400拷贝/ml以上、近一次CD4细胞计数<200个/μl是HIV感染配偶抗体阳转的影响因素。  相似文献   

17.
18.
The human immunodeficiency virus type-1 (HIV-1) vaccine candidate F4/AS01 has previously been shown to induce potent and persistent polyfunctional CD4+ T-cell responses in HIV-1-seronegative volunteers. This placebo-controlled study evaluated two doses of F4/AS01 1-month apart in antiretroviral treatment (ART)-experienced and ART-naïve HIV-1-infected subjects (1:1 randomisation in each cohort). Safety, HIV-1-specific CD4+ and CD8+ T-cell responses, absolute CD4+ T-cell counts and HIV-1 viral load were monitored for 12 months post-vaccination. Reactogenicity was clinically acceptable and no vaccine-related serious adverse events were reported. The frequency of HIV-1-specific CD4+ T-cells 2 weeks post-dose 2 was significantly higher in the vaccine group than in the placebo group in both cohorts (p < 0.05). Vaccine-induced HIV-1-specific CD4+ T-cells exhibited a polyfunctional phenotype, expressing at least CD40L and IL-2. No increase in HIV-1-specific CD8+ T-cells or change in CD8+ T-cell activation marker expression profile was detected. Absolute CD4+ T-cell counts were variable over time in both cohorts. Viral load remained suppressed in ART-experienced subjects. In ART-naïve subjects, a transient reduction in viral load from baseline was observed 2 weeks after the second F4/AS01 dose, which was concurrent with a higher frequency of HIV-1-specific CD4+ T-cells expressing at least IL-2 in this cohort. In conclusion, F4/AS01 showed a clinically acceptable reactogenicity and safety profile, and induced polyfunctional HIV-1-specific CD4+ T-cell responses in ART-experienced and ART-naïve subjects. These findings support further clinical investigation of F4/AS01 as a potential HIV-1 vaccine for therapeutic use in individuals with HIV-1 infection.  相似文献   

19.
《Vaccine》2018,36(46):7025-7032
IntroductionIn sub-Saharan Africa, a generation of HIV-1-infected children is approaching the age of sexual debut and becoming at risk for HPV infection and its sequelae. We assessed safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in HIV-1-infected adolescents.MethodsIn an open-label trial among Kenyan, HIV-1-infected adolescents aged 9–14 years, we administered the qHPV vaccine at 0, 2 and 6 months and measured antibody titers to HPV-16, 18, 6 and 11 at month 7 and 12 post-vaccination. Measures of immunogenic response from HIV-1-negative historical cohorts from Africa and HIV-1 positive adolescent cohorts from the USA were used for comparison.ResultsWe enrolled 100 girls and 80 boys with a median age of 12 years and median baseline CD4 cell count of 684 (IQR 478, 935) cells/µL. One hundred and fifty four (86%) were receiving antiretroviral therapy for a median of 4.5 (IQR 2.3, 6.3) years; 110 (71%) had <400 copies of plasma HIV-1 RNA/mL. Of 189 enrolled children, 179 received all three doses. Two hundred and eighty five (64%) of 445 adverse events were injection site reactions; none were greater than grade 2. Of 6 Serious Adverse Events (SAEs), none were considered vaccine related. Seroconversion to HPV-18, 16, 11, 6 at month 7 occurred in 93.3%, 98.3%, 97.2% and 99.6% of vaccine recipients; similar rates have been reported in historical controls. The mean log10 HPV antibody titer measured at month 7 increased with each log10 increase in CD4 by 1.4 (95% CI: 1.1–1.7) for HPV-18; 1.2 (0.9–1.4) for HPV-16; 1.1 (0.8–1.3) for HPV-11; 0.7 (0.5–1.0) for HPV-6 (all p < 0.0001).ConclusionAlmost all Kenyan HIV-1-infected adolescents mounted an immune response comparable to other immunized populations. HPV antibody titers were higher in those with preserved CD4 cell counts. Longer term-follow up will determine sustainability of the immune response.ClinicalTrials.gov number, NCT00557245.  相似文献   

20.
《Vaccine》2022,40(32):4496-4502
BackgroundVery limited data are available on the persistence of rubella antibodies in vertically HIV-infected individuals who were vaccinated early in life.MethodsProspective, cohort study on 4 groups of patients: 96 vertically HIV-1-infected individuals (v-HIV), 69 horizontally HIV-1-infected individuals (h-HIV), 93 healthy controls previously vaccinated for rubella (vac-CON) and 20 healthy controls with history of rubella disease (dis-CON). A blood sample was collected and rubella antibodies were analyzed by ELISA. Rubella antibodies above 10 IU/mL were considered protective. Individuals with seronegative results were offered an extra MMR vaccine dose and were tested at least 30 days afterwards.ResultsTime since previous rubella vaccination was similar in v-HIV, h-HIV and vac-CON (16, 11 and 11 years; p = 0.428). v-HIV and h-HIV were also comparable regarding median CD4 T cells (613 and 614 cells/mm3; p = 0.599) and percentage on ART (93.8% and 98.6%; p = 0.135) at study entry. v-HIV had less individuals on virological suppression (63.5%) compared to 85.5% in h-HIV (p < 0.001). Rubella seropositivity and antibodies were significantly lower in v-HIV compared to h-HIV (32.3% vs 65.5%, 4.3 IU/mL vs 21.1 IU/mL; p < 0.001). Time interval between the last rubella vaccine dose and study entry was associated with an increase of rubella seronegativity, with a 7% higher chance of seronegativity for each one-year increase. After an extra MMR dose, 40 out of 48 (83.3%) seronegative individuals responded, with no significant difference among groups considering rubella seropositivity and antibody levels.ConclusionAs vertically HIV-infected individuals reach adolescence and adulthood, assessment of vaccine antibodies can identify those who might benefit from an extra vaccine dose.  相似文献   

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