ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo explore the possibility of gene therapy of HIV infection based on the multiple antiretroviral activities of interferon (IFN)-β.DesignWe introduced into HIV target cells an IFN-β gene placed under an expression control ensuring a low, and constitutive expression, sufficient to confer a permanent antiviral state without impeding normal cell function.MethodsWe transformed, with an efficacy ranging from 20–55%, peripheral blood lymphocytes (PBL) derived from healthy, seronegative donors, and from asymptomatic HIV-infected individuals by the HMB-KbHulFNβ retroviral vector carrying the human IFN-β coding sequence driven by a fragment of the murine H-2Kbgene promoter.ResultsThe replication rate of the IFN-β-expressing cells was no different from that of untransformed controls during the 21-day period ofin vitroobservation. When IFN-β-transformed, purified CD4+ lymphocytes from healthy donors were HIV-1LAI-infected, virus replication was inhibited, and most of the cells survived, in contrast to untransformed CD4+ cells which were all destroyed 12 days after infection. Protection of CD4+ cells from the same donors was also observed in suspensions of IFN-β-transformed total PBL that were infected with HIV-1LAI. In IFN-β-transformed PBL from four HIV-infected donors, endogenous HIV replication was decreased, and 28–69% of the CD4+ cells survived at the end of the 21 days in culture. In the untransformed control PBL suspensions, all CD4+ cells were destroyed. In long-term experiments, HIV-infected, IFN-β-transformed cell populations of the lymphocytic CEM, and the promonocytic U937 line were kept in culture for 60 days, during which time they remained resistant to HIV infection.ConclusionThese results indicate that further exploration of autocrine IFN-β production for somatic cell gene therapy of HIV infection is warranted.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveAll the conserved regions of HIV gp120 have at least some partial homology with human leukocyte antigen (HLA) class I or class II. One functional similarity is the ability of gp120, and HLA class II to bind CD4. Given the close association between HIV-induced disease, and the amount of immune activation, and anergy, features closely associated with chronic allogenic stimulation, we asked whether gp120 shared any other properties of HLA, in this case the ability to bind peptides.DesignT-cell epitope peptides known to bind to soluble HLA class I or class II were photolabelled, and made radioactive. Cross-linking of modified peptides to soluble HLA class I, II, and gp120 was activated by ultraviolet light, and analysed by sodium dodecylsulphate-polyacrylamide gel electrophoresis.ResultsA signal peptide binding to HLA class I, and a haemagglutinin peptide that binds to HLA class II were found to bind soluble gp120 specifically; binding, and cross-linking could be competed out with excess of the unmodified peptides but not unrelated control peptides. Molecular modelling of gp120 suggests shared anchor sites for peptides binding to both HLA, and gp120 soluble molecules.ConclusionsThe ability to bind these two peptides suggests that gp120 has a peptide-binding site of broad specificity, which if functionalin vivo, could compete with normal peptide loading of major histocompatibility complex (MHC) class I and/or class II peptides, as well as aberrantly stimulate the T-cell receptor (by virtue of its potential to be mistaken for an allogenic MHC/peptide complex), resulting in immune activation, anergy, and apoptosis in susceptible hosts.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo explore the possibility that an HIV-1 gene product may modulate entry of an invasive enteric pathogen into a terminally differentiated human intestinal cell line. HIV-1 Tat was selected for investigation because of its unique ability to cross cell membranes.MethodsAfter transient transfection of HT29-C1 cells with plasmids containing HIV-1 long terminal repeat (LTR)-lacZplus a Tat expression cassette, or with a pSR-lacZcontrol plasmid, bacterial invasion assays were performed on both groups of cells utilizing a clinicalSalmonellaisolate. Assays were performed concurrently on a control group of non-transfected cells. A second series of experiments compared bacterial invasion into cells transfected with the Tat expression vector alone versus cells transfected with either an isogenic expression vector that did not make Tat, or with pSR-lacZFinally, the ability of exogenous Tat protein to transactivate an HIV-1 LTR-chloramphenicol acetyltransferase (CAT) plasmid which had been transfected into HT29-C1 cells, and to modulateSalmonellainvasion was also assessed.ResultsHT29-C1 cells transfected with a Tat expression vector, either alone or in combination with another plasmid, were significantly less susceptible to bacterial invasion than cells that either did not undergo transfection, were transfected with an otherwise isogenic expression vector without Tat, or transfected with an unrelated plasmid. Duplicate experiments also demonstrated that exogenous purified Tat protein transactivated an HIV-1 LTR-CAT plasmid which had been transfected into HT29-C1 cells, and inhibitedSalmonellainvasion compared with unexposed cells.ConclusionHIV-1 Tat inhibitsSalmonellainvasion of a human enterocyte cell line whether the protein is expressed intracellularly or provided exogenously.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo construct, and evaluate a decision analytic model of proposed management strategies for HIV-infected patients presenting with cerebral mass lesions, radiographically compatible with toxoplasmosis, lymphoma, or other etiologies, assuming knowledge ofToxoplasmaantibody status in serum.MethodsUsing decision analysis, we evaluated two management strategies, for patients found to be eitherToxoplasma-seropositive or -negative, for whom an initial choice was made for early brain biopsy (EB) or for empiric therapy with delayed biopsy (ETDB) of non-responders. The outcome to be optimized was the percentage of patients alive at 12 months. Model variables included predictive value of toxoplasmosis serology, probabilities of treatment response, and death within 14–21 days conditional on correct diagnosis, probability of operative death, probabilities of non-diagnostic brain biopsy conditional both on correct diagnosis, and prior treatment.ResultsOne, and two-way sensitivity analyses, byToxoplasmaserostatus, led to the following conclusions (1) forToxoplasma-seropositive patients, ETDB gives nearly equivalent outcomes to EB of all patients; (2) forToxoplasma-seronegative patients, although both strategies have equivalent outcomes under baseline assumptions, EB is preferred if there are even small survival advantages for early versus delayed diagnosis of lymphoma or other conditions, or if risk of death within 14–21 days of ET exceeds 10% when correct diagnosis is not toxoplasmosis.ConclusionUnder plausible assumptions,Toxoplasma-seronegative patients will benefit from an early biopsy strategy.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo determine autopsy-proven causes of death in HIV-infected patients treated for tuberculosis in Abidjan, Côte d'lvoire.MethodsA computerized listing of 9523 patients diagnosed with tuberculosis, and tested for HIV infection at Abidjan's two large tuberculosis treatment centers from July 1989 to December 1991 was matched against a listing of 496 patients who were autopsied in Abidjan's largest public hospital in 1991–1992.ResultsFifteen matching patients were identified including 11 adults with smear-positive pulmonary tuberculosis, three adults with extrapulmonary tuberculosis, and one child with smear-negative pulmonary tuberculosis. The autopsy-proven causes of death among the adults were tuberculosis (n = 4), bacterial infections (n = 3), cerebral toxoplasmosis (n = 2), pulmonary nocardiosis (n = 2),Pneumocystis cariniipneumonia (n = 1), atypical mycobacteriosis (n = 1), and wasting syndrome (n = 1). Tuberculosis was the primary cause of death in two of five smear-positive patients who had not completed therapy, in none of the six patients with smear-positive disease who had completed therapy, and in two of the three patients with extrapulmonary tuberculosis.ConclusionsChemoprophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) might have provided benefit to eight (57%) of the 14 adults in this series who died either of bacterial infections, toxoplasmosis, nocardiosis, or pneumocystosis. Prospective studies are required to elucidate further the causes of increased mortality, and to evaluate the benefits of TMP-SMX prophylaxis in HIV-infected African patients with tuberculosis.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo determine the risk of developing high grade anal squamous intraepithelial neoplasia (HG-AIN) in relation to HIV infection, and immunosuppression, after controlling for the effects of human papillomavirus (HPV) infection.DesignProspective cohort study of 158 HIV-seropositive, and 147 HIV-seronegative homosexual men presenting to a community-based clinic with initially negative anal cytologic, and colposcopic findings.MethodsSubjects completed self-administered questionnaires, underwent cytologic screening, and standardized unaided, and colposcopic examination of the proximal anal canal for presence of abnormalities suggestive of AIM. Anal specimens were screened for HPV DMA.ResultsHG-AIN developed in eight (5.4%), and 24 (15.2%) HIV-seronegative, and -seropositive men, respectively. Risk of HG-AIN among HIV-seronegative men was associated with detection of anal HPV types 16 or 18 by Southern transfer hybridization (STH), detection of HPV 16 or 18 at the lower levels by polymerase chain reaction but not by STH, and with number of positive HPV tests; HG-AIN risk among HIV-seropositive men was associated with detection of HPV 16 or 18 only by STH, detection of HPV types other than 16 or 18, CD4 count ≤ 500 × 106/l, and number of positive HPV tests. HIV-induced immunosuppression remained an independent predictor of HG-AIN after adjusting for type, and level of detection of HPV; HIV infection predicted HG-AIN risk after adjustment for number of positive HPV tests.ConclusionsThe association of HG-AIN with HIV, independent of HPV type, level of HPV detection, and number of positive HPV tests, suggests that this increased risk cannot be entirely explained by an effect of HIV on HPV detection. Future studies focusing on factors more specific to the local microenvironment in the anal canal should help clarify these issues.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo assess the likely impact on HIV incidence of increased condom use, a reduction in casual sexual partners, treatment programmes for other sexually transmitted diseases (STD), and combinations of these in rural Uganda.MethodsA simulation model for the transmission dynamics of HIV infection, and STD was employed, drawing on data from a rural population cohort in South-West Uganda with an HIV prevalence of 9% among adults in 1990.ResultsFor the scenario most consistent with data from the study population, 39% of all adult HIV infections were averted, in the 10 years from 1990, when condoms were used consistently, and effectively by 50% of men in their contacts with one-off sexual partners (such as bar girls, and commercial sex workers). Reducing by 50% the frequency of men's sexual contacts with one-off partners averted 68% of infections. Reducing by 50% the duration of all STD episodes averted 43% of infections. Combining these three interventions averted 82% of all adult infections in the 10 years from 1990.ConclusionA substantial proportion of HIV infections may be averted in general populations through interventions targeted only on less regular sexual partnerships.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesTo assess the effectiveness of an intervention for providing information, and support to HIV-positive donors on changes in their sexual behavior, and to assess which donor characteristics are predictive of behavior change.DesignSubjects were randomly assigned to a structured intervention or community referral group. Follow-up assessments were conducted every 6 months.SettingNew York City, New York, USA.ParticipantsA cohort of 271 HIV-infected persons who donated blood to the New York Blood Center.InterventionDonors randomized to the structured intervention program met individually with a nurse for counseling, and were offered a six-session support group. The program was designed to provide information, encourage safer sexual behavior, and provide support.Main outcome measuresSexual behavior, psychological distress, and psychological help seeking, and immune function.ResultsIn both groups there was a large decrease over time in reports of unsafe sexual activity. However, more than 30% of participants in both groups reported unsafe sexual activity at the 1-year follow-up visit. Donors randomized to the structured intervention program did not report significantly more behavior change at the 1-year follow-up.ConclusionsBetter programs to promote behavior change in seropositive individuals are needed.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesTo ascertain the level of acceptance of a prophylactic HIV vaccine trial in high-risk HIV-seronegative heterosexual cohorts of men, and women in Mombasa, Kenya, and to assess the anticipated effects of participation on risk behavior.MethodsStandardized questionnaire administered to a convenience sample of commercial sex workers, and trucking company employees enrolled in prospective cohort studies.ResultsNinety-six per cent of respondents believed that HIV was a major problem in Kenya, and 86% of men, and 94% of women perceived themselves at risk. One hundred per cent of women, and 84% of men expressed interest in participation in an HIV vaccine trial, after explanation of the experimental nature of the vaccine, double-blind placebo-controlled design, prolonged follow-up, and potential change in serostatus. Seventeen per cent of men, and 9% of women anticipated an increase in risk behavior as a result of participation.ConclusionThe majority of individuals in two high-risk cohorts were interested in participating in Phase III efficacy trials of HIV vaccines. A significant minority anticipated an increase in risk behavior, which emphasizes the need for intensive counseling, and education throughout a vaccine trial.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID