ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To develop effective, specific and safe anti-idiotypic antibody (Ab2) vaccines against HIV-1.Design:Murine monoclonal Ab2 were generated against anti-HIV-1 antibody 0.5β (Ab1), which binds to gp120, neutralizes HIV-1 and inhibits virus-induced syncytia formation.Methods:Mice were immunized with Ab1, and Ab2 were produced from immunized mice by the hybridoma technique. The Ab2 were characterizedin vitro, injected into rabbits, and the anti-anti-idiotypes (Ab3) induced in the rabbits were analyzed for binding and antiviral reactivities by enzyme-linked immunosorbent assay, p24gagrelease and syncytia formation assays.Results:Seven Ab2 bound to the antigen-combining site of Ab1, one of which (UD7) induced Ab3 in rabbits that were Ab1-like in their binding reactivities to PB1 (recombinant gp120 fragment) or peptides of gp120, and shared idiotypes with the Ab1. Crude Ab3-containing sera specifically and effectively neutralized the virus.Conclusion:Monoclonal Ab2 UD7 has potential as a vaccine against HIV-1.AIDS 1993,7:1553–1559

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To compare biologic properties of HIV-1 isolates from children with and without AIDS as a measure of viral cytopathogenicity.Patients and participants:Virus isolates from peripheral blood mononuclear cells of 13 perinatally infected children were compared for specificin vitrobiologic properties.Methods:Virus isolates were examined for biologic properties as measured by their ability to infect H9 cells and to induce syncytia in susceptible cells.Results:Most of the pediatric HIV-1 isolates failed to infect CD4+ H9 cells and induce syncytia in susceptible cells, regardless of whether they were from children with or without AIDS. All of the isolates, however, grew well in mitogen-stimulated normal adult lymphocytes. These results are in contrast to those with HIV-1 isolates from adults, whose biologic properties were related to the stages of the disease.Conclusions:These results indicate that, unlike adult HIV-1 isolates, the biologic properties of pediatric isolates are not related to the stages of the disease. The rapid development of disease in children may therefore be due to factors other than intrinsic properties of HIV-1 strains present in children.AIDS 1993,7:1561–1564

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To evaluate a manual method (Cytosphere) for quantifying CD4+ T-cell numbers.Design:Cross-sectional study of HIV-1-seronegative and HIV-1-seropositive individuals evaluated for absolute CD4 counts by both standardized flow cytometric measurements and manual Cytosphere technology using a hemacytometer.Setting:University research hospitals in both the United States and Africa.Patients, participants:Blood specimens from 382 patients were evaluated. These were broken down into 294 samples obtained from HIV-1-seropositive patients and 88 samples obtained from HIV-1-seronegative patients.Interventions:None.Outcome measured:Absolute CD4 cell number.Results:Evaluation of samples obtained from HIV-1 patients in both the United States and Africa demonstrated an overall correlation of the Cytosphere assay with flow cytometry of 0.912 (95% confidence interval, 0.895–0.928;P<0.001). When samples were stratified based on CD4+ T-cell counts determined by flow cytometry, the Cytosphere assay had a 96% predictive value for correctly identifying individuals with CD4 T-cell counts > 200×106/l and a 92% predictive value for correctly identifying individuals with CD4 T-cell counts < 200×106/l.Conclusions:This assay appears to have the potential for the quantitation of CD4 cells in the limited laboratory facilities in developing countries and to have a strong correlation with standard flow cytometric technology.AIDS 1993,7:1565–1568

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Background:HIV disease is epidemic in Africa, but associated mortality, underlying pathology and CD4+ T-lymphocyte counts have not previously been evaluated in a representative study. Such data help to determine the management of HIV-positive people. Both HIV-1 and HIV-2 infections are prevalent in Côte d'lvoire, and the pathology of HIV-2 infection in Africa is unclear.Methods:Consecutive adult medical admissions to a large city hospital in Côte d'lvoire were studied in 1991, and a sample of HIV-positive deaths autopsied.Results:Of 5401 patients evaluated, 50% were HIV-positive; 38% of these died, with a median survival of 1 week. At autopsy (n=294, including 24% of HIV-positive deaths in hospital), tuberculosis (TB), bacteraemia (predominantly Gram-negative rods) and cerebral toxoplasmosis caused 53% of deaths. TB was seen in 54% of cadavers with AIDS-defining pathology andPneumocystispneumonia in 4%. The median CD4+ T-lymphocyte counts in those who died was <90×106/l. Compared with HIV-1-positives, patients with HIV-2-positivity had a greater frequency of severe cytomegalovirus infection, HIV encephalitis and cholangitis.Conclusions:In this population, HIV-positive adults present to hospital with advanced disease associated with high mortality. The three major underlying pathologies (TB, toxoplasmosis and bacteraemia) are either preventable or treatable. TB is an underestimated cause of the 'slim' syndrome in Africa. The patterns of pathology in HIV-2-positive patients suggest a more prolonged terminal course compared with HIV-1. There is an urgent need for attention towards the issues of therapy and care for HIV disease in developing countries.AIDS 1993,7:1569–1579

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To investigate penetration of zidovudine (ZDV) into the cerebrospinal fluid (CSF) of HIV-infected patients for whom a lumbar puncture was indicated.Design:A prospective study.Setting:General 525-bed hospital with special funding for treatment and research of HIV-infected patientsPatients, participants:Thirty-nine patients with a medical indication for lumbar puncture who used ZDV chronically were included in this study (50 samples in total).Main outcome measure:Determination of ZDV and proteins in CSF and plasma samples.Results:CSF concentrations of ZDV showed little fluctuation 1–8 h after the last ingestion of ZDV. In contrast, plasma levels displayed large variability in this period and decreased exponentially over time. As a result, the CSF/plasma ratio increased linearly over time. No significant relation between the ZDV dose, neither the medical indication for lumbar puncture nor the protein ratio (as a measure for the integrity of the blood–brain barrier), and CSF levels of ZDV was found. The CSF/plasma ratio of ZDV did not give essential information on drug distribution into CSF.Conclusions:Penetration of ZDV into the CSF appears to be independent of the dose (range, 200–1250 mg daily), which may be an explanation for the efficacy of low doses of ZDV in the prevention and treatment of HIV-related neurological diseases. ZDV levels were at steady-state during the first 6 h after ingestion. The CSF/plasma ratio of ZDV concentrations is not an appropriate marker for drug penetration into CSF.AIDS 1993,7:1581–1587

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The pathogenesis of neurologic and neuropsychologic dysfunction in HIV-1 infection is unclear. The purpose of the study was to determine an association between cerebral perfusion and HIV-1-related ocular microangiopathic syndrome.Methods:We studied 28 HIV-1-infected patients, seven of whom presented with asymptomatic HIV infection, nine with lymphadenopathy syndrome or AIDS-related complex, and 12 with AIDS. Cerebral perfusion was semiquantitatively measured by single photon emission computed tomography of the brain using technetium-99 hexamethyl-propylenamine oxime (HMPAO-SPECT). The conjunctival manifestation of HIV-1-related microangiopathic syndrome was measured by a rating scale determining blood-flow sludging and by counting retinal cotton-wool spots. CD4 count, neopterin, β2-microglobulin (β2M), haemoglobin, and age were determined as putative confounding variables.Results:Mean conjunctival sludge in patients with normal HMPAO-SPECT findings was 1.3±0.5 (mean±s.e.m.); no cotton-wool spots were present. In patients with slightly impaired HMPAO-SPECT, it was 2.1±0.6 and mean cotton-wool spot count was 1.1±0.4. In patients with severely impaired HMPAO-SPECT, mean conjunctival sludge was 4.5±0.3 and mean cotton-wool spot count was 4.9±1.1 HMPAO-SPECT findings were closely associated with conjunctival sludge (r=0.72;P<0.001) and number of cotton-wool spots (r=0.78;P<0.001), whereas only a slight association with staging of HIV disease was found (P=0.052). Analysis of covariance controlling for CD4 count, neopterin, β2M, age, and haemoglobin demonstrated a significant difference between the three HMPAO-SPECT groups for both the number of cotton-wool spots (P<0.001) and the conjunctival sludge rating (P<0.001).Conclusion:There was a close association between severity of HIV-1-related ocular microangiopathic syndrome and severity of cerebral hypoperfusion. Microvascular alterations might contribute to the pathogenesis of neurological and neuropsychological symptoms in patients with HIV-1 disease. Furthermore, the conjunctival sludge rating and the number of cotton-wool spots might be appropriate indicators for severity of microvascular changes of the central nervous system.AIDS 1993,7:1589–1594

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:We measured micronutrient values in patients with the HIV wasting syndrome and in other HIV-seropositive patients to determine whether specific micronutrient deficiencies were associated with the wasting syndrome.Methods:Serum from 47 HIV-seropositive patients was evaluated for concentrations of vitamin A, B6, B12, C, D, E, folate, the mineral zinc, carotene and glutathione. Comparisons were made between groups stratified by CD4 cell count and wasting/non-wasting status.ResultsMean serum levels were significantly lower for vitamin A (P=0.04), folate (P=0.04) and carotene (P=0.06) in patients with the HIV wasting syndrome than in non-wasting patients with comparable CD4 cell counts. Values of vitamins A, B6, C, D, carotene and glutathione were below the normal range in over 10% of HIV-seropositive patients in this study.ConclusionDecreased micronutrient concentrations are common in HIV-infected patients and occur more frequently in patients with the wasting syndrome. Clinicians may wish to evaluate HIV-seropositive patients with wasting for individual micronutrient deficiencies, although they should note that particular deficiencies may be only part of the larger picture of malabsorption and undernutrition.AIDS 1993,7:1595–1600

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To determine the impact of HIV-1 infection on thymocyte development, and the role of thymic infection on the pathogenesis of neonatal HIV-1 infection.Design and methods:The consequences of thymic infection by HIV-1 were examined by comparative histologic and molecular analyses of an asymptomatic, HIV-1-seropositive 3-day-old subject, versus age- and treatment-matched controls. The presence of replicating virus was established byin situhybridization with specific molecular probes to HIV-1. The distribution of thymocyte subsets was determined by quantitative flow cytometry following staining with antibodies to CD4 and CD8 cell surface proteins.Results:The results show clear evidence of severe thymic involution, HIV-1 infection of thymocytes, and selective depletion of thymocyte subpopulations. The consequences of HIV-1 infection were a marked depletion of CD3+CD4+CD8hiand CD3+CD4+CD8−cells. The phenotype of the residual thymic lymphoid population was predominantly that of immature CD3−CD4−CD8−double negative and CD3+CD4+CD8locells.Conclusion:Changes in the distribution of thymocyte subsets suggests a role for thymic involvement in the pathogenesis of HIV-1 infection in neonates.AIDS 1993,7:1601–1605

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To examine the stability of cognitive function in patients with asymptomatic HIV infection.Design:Previous longitudinal studies of cognitive function have focused on patients who progress in terms of disease stage. The present study avoided this potential confounding factor by including only subjects who remained in the asymptomatic stage of infection over the follow-up period.Method:Subjects were administered an extensive neuropsychological test battery at baseline and 1 year follow-up. Overall performance was characterized as normal or abnormal based on the performance of a well-matched HIV-negative control group.Results:A significantly higher proportion of HIV-positive subjects became abnormal at the follow-up examination. Comparison of the seropositive subjects who remained normal with those who became abnormal revealed no differences at baseline on age, education, depression or CD4 levels. Subjects who became abnormal had worse performance at baseline on measures of information processing, verbal learning and memory, and reaction time.Conclusions:These data indicate that cognitive function may decline in some patients who continue to be in the asymptomatic stage of infection. Patients with a pattern of cognitive abnormalities at baseline, which includes information processing and reaction time deficits, may be at increased risk for declines in function during early stages of infection.AIDS 1993,7:1607–1611

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID