ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo study the degree of immunogenicity of each HIV-1 protein.DesignIn most viral systems, antiviral cytotoxic T-lymphocytes (CTL) from a given donor preferentially recognize only one or a small number of viral proteins.MethodsAnti-HIV CTL were generated byin vitrostimulation of peripheral blood mononuclear cells from seropositive donors and tested against multiple HIV-1 proteins or groups of proteins encoded by seven genes (env, gag, pol, nef, rev, tatandvif). Using autologous target cells infected with recombinant vaccinia viruses expressing one of the HIV-1LA1proteins, we compared the cytolytic activities obtained from bulk culture with those found in limiting dilution analysis (LDA).ResultsOur results were noteworthy for the following reasons. (1) Each responding donor reacted simultaneously to multiple proteins; this is very unusual in other viral systems. Anti-Gag CTL were detected in most, and anti-Pol in approximately three-quarters, of the patients, together with very high amounts of the corresponding CTL precursors in LDA. CTL against Env and Nef were found in two-thirds of the patients, while Vif- and Rev-specific CTL were less frequent. Finally, Tat was seldom recognized by CTL, but its antigenicity was revealed in LDA. (2) All responding cells revealed in bulk cultures as well as in LDA were CD8+ T-cells, and theirin vitrodifferentiation did not require the help of CD4+ T-cells. (3) Proteins from the HIV-1LA1isolate were recognized with high frequency by CTL from seropositive donors, most certainly being infected by other isolates, which suggests that relatively conserved epitopes are predominant targets of CTL.ConclusionTaken together, these results are encouraging for vaccine purposes, since anti-HIV-1 CTL stimulation is thought to be a requirement for such a vaccine.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo determine which parameters are associated with clinical progression during zidovudine treatment of asymptomatic HIV-1-infected individuals.MethodsTwenty-four initially asymptomatic HIV-1-infected individuals were treated with zidovudine and followed until the development of AIDS or for approximately 3 years. HIV-1 phenotype was determined by cocultivation of patient cells with donor lymphocytes, and by a new assay of direct cocultivation with MT-2 cells. Specific mutations in the HIV-1 reverse transcriptase (RT) gene conferring resistance to zidovudine were detected using a selective polymerase chain reaction.ResultsProgression to AIDS was more rapid in individuals harbouring syncytium-inducing (SI) viral isolates or showing a conversion from non-syncytium-inducing (NSI) to SI viral isolates. One out of 20 patients who spent a total of 559 months harbouring an NSI phenotype progressed to AIDS, whereas eight out of 12 patients who spent a total of 223 months harbouring an SI phenotype progressed to AIDS (P<0.001). There was no significant difference between SI and non-SI isolates in the frequency of five mutations causing zidovudine resistance. However, all SI isolates obtained after 2 years of treatment contained mutations in codons 41 and 215 of the RT gene, whereas only five out of 11 (45%) NSI isolates obtained at that time had this combination of mutations.ConclusionsConversion to the SI phenotype cannot be prevented by zidovudine treatment. The presence or appearance of an SI virus heralded disease progression in zidovudine-treated individuals. Further research is required to investigate the relationship between virus phenotype and development of zidovudine resistance.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo evaluate the diagnostic and prognostic value of serum tumor necrosis factor-α (TNF-α) levels in HIV-1-infected children.DesignSerum levels of TNF-α were evaluated in 57 HIV-1-infected symptomatic children aged between 7 months and 8 years.MethodsTNF-α levels were determined by enzyme immunoassay. The sensitivity of the assay was 10pg/ml.ResultsTNF-α levels (mean ± s.d.) were significantly elevated in HIV-1-infected patients (285 ± 390 pg/ml), compared with HIV-1-uninfected age-matched controls (22.7 ± 4.9 pg/ml). Among HIV-1-infected children the highest levels of TNF-α were noted in those withMycobacterium avium intracellulare(MAI) infection and those with interstitial lymphoid pneumonitis (LIP). In contrast, patients withPneumocystis cariniipneumonia, progressive encephalopathy or cachexia did not have markedly elevated TNF-α levels.ConclusionsSerum TNF-α is increased in symptomatic HIV-1-infected children, with higher levels in children with LIP or MAI. Serum TNF-α levels are not diagnostic for cachexia or progressive encephalopathy.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo measure diurnal variation in the CD4 cell count and T-cell reactivity of drug users.DesignA prospective epidemiological study among HIV-infected and non-infected drug users attending the Municipal Health Service of Amsterdam, The Netherlands.PatientsEleven HIV-infected and seven non-infected drug users.Main outcome measuresCD4 cell counts and T-cell reactivity three times a day. T-cell subsets and T-cell reactivity were determined from blinded samples within 2 hours.ResultsThe number of CD4 cells increased by 130 $$ 106/I (P < 0.05) in HIV-infected intravenous drug users over 8 hours. Following stimulation with anti-CD3 monoclonal antibodies, the T-cell reactivity of HIV-infected drug users rose from 118 to 221 c.p.m. (P < 0.01) over 8 hours. CD4 cell counts of the total study population increased by 37% and T-cell reactivity by 93%. The increase in the number of CD4 cells was more marked among active drug users than among drug users who had not used drugs recently.ConclusionVariation in the CD4 cell count and in T-cell reactivity is large among drug users.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo determine the frequency of Epstein-Barr virus (EBV) oropharyngeal shedding during HIV infection in homosexual men in the Multicenter AIDS Cohort Study.DesignThe cohort consisted of 210 men who were HIV-seronegative at their baseline study visit, 39 of whom seroconverted to HIV at a later date, and 73 asymptomatic and mildly symptomatic men with HIV infection of indeterminate duration.MethodsEBV in throat washings was detected by transformation of newborn cord blood lymphocytes.ResultsEBV was isolated from 49% (35 out of 71) of the HIV-seropositive and 16% (33 out of 204) of the HIV-seronegative homosexual men tested at their baseline visit. Elevated EBV shedding frequency was noted 6 months before, as well as during the first HIV-seropositive clinic visit, in the men who seroconverted to HIV. Seronegative men who shed EBV at their baseline visit seroconverted to HIV within a shorter period than did non-shedders during 5 years of follow-up. Shedding of EBV was not significantly associated with either abnormal T-cell numbers, clinical symptoms or risk for development of AIDS.ConclusionsThere is an increased rate of EBV shedding in HIV-seropositive homosexual men that occurs very early in the course of HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo develop a useful system for evaluating novel anti-HIV drugs.DesignThe activity of most antiviral compounds in cell-free HIV infection systems has been evaluted. However, the inhibitory effects on both the process of HIV induction and viral dissemination to uninfected cells have not been fully investigated. We have therefore developed a new cocultivation system using chronically HIV-infected monocytes and CD4+ T-lymphocytes in the presence of tumor necrosis factor (TNF).MethodsWe designed a cocultivation system using flow cytometry with U1 cells and Molt-4 cells in the presence of TNF. The antiviral activities of several compounds in the cocultivation system and other assay systems were compared.ResultsOnly pradimicin A and glycyrrhizin showed strong inhibitory activity in the cocultivation system in the presence of TNF, whereas dextran sulfate, curdlan sulfate and N-acetylcysteine exhibited moderate or weak inhibitory activity in the system. 3'-azido-2', 3'-dideoxythymidine and 2', 3'-dideoxyadenosine were completely ineffective in the system.ConclusionThese results support the suggestion that our cocultivation system includes HIV induction in chronically infected monocytes, and the resulting cell-to-cell infection between HIV-infected monocytes and Molt-4 cells or Molt-4 cells and their HIV-converted counterparts. Our new cocultivation system may constitute a useful tool in the identification of novel anti-HIV compounds.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo assess the frequency of mycoplasma infections in HIV-antibody-positive and -negative individuals by studying the serological responses against mycoplasmas, especiallyMycoplasma fermentansandM. pirum.DesignAn enzyme-linked immunosorbent assay (ELISA) was used to measure immunoglobulin G (IgG) class antibody concentrations against six mycoplasma species in sera of HIV-positive and HIV-negative individuals.MethodsSerum samples were obtained from 30 HIV-positive individuals (10 asymptomatics, 10 with lymphadenopathy syndrome and 10 with AIDS), 10 HIV-negative partners of HIV-positive individuals and 40 HIV-negative blood donors. Antibodies toM. fermentansstrainsincognitusand PG18,M. pirum, M. genitalium, M. pneumoniaeandM. hominiswere assessed by immunoblot or ELISA. Absorbance values were taken as a semiquantitative measurement for antibody concentration and an arbitrary cut-off value (0.8) was set to establish seroprevalence.ResultsThere was no significant difference in the mean IgG concentrations of any of the six mycoplasmas between HIV-positive and HIV-negative groups. Antibody concentrations were also similar in different clinical phases of HIV infection. Antibody concentrations to different mycoplasma strains were compared with each other to reveal eventual cross-reactions caused by shared antigens; the strongest correlation (r = 0.836) was found betweenM. fermentansstrainsincognitusandM. pirumantibody concentrations. The correlation betweenM. fermentansstrainsincognitusand PG18 was also significant but weaker (r = 0.522). No shared antigens betweenM. fermentansstrainincognitusandM. pirumwere demonstrated by immunoblot.ConclusionsAntibodies againstM. fermentanstype strain PG18, strainincognitusand againstM. pirumare detected infrequently and their presence does not correlate with HIV infectionper seor with the clinical stage of HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo describe a localized form ofMycobacterium avium intracellulare(MAI) infection occurring concurrently with the restoration of cutaneous delayed-type hypersensitivity (DTH) responses to mycobacterial antigens after commencement of ziclovudine therapy in immunodeficient HIV-infected patients.PatientsThe first 108 Western Australian patients with a CD4+ T-cell count of <200 $$ 106/1 and/or symptomatic disease to be given zidovudine (ZDV), of whom 72 had adequate DTH data.MethodsDTH responses to seven antigens were measured by the 'Multitest' method before and on at least two occasions during the 6 months after commencing ZDV. All patients were reviewed at regular intervals and clinical events recorded.ResultsOf the 64 patients who were anergic to tuberculin before commencing ZDV, 27 (42%) developed a DTH response to tuberculin after ZDV. Four of the nine patients with a ‘Multitest’ tuberculin response of ≥8mm and one patient who developed a positive Mantoux test toM. aviumpurified protein derivative developed an illness characterized by localized MAI infection, lymphadenopathy and/or severe fevers after 1–2 weeks.ConclusionThe development of localized MAI infection and/or fevers shortly after commencing ZDV in immunodeficient HIV-infected patients may reflect restoration of cellular immunity to mycobacterial antigens in some patients rather than early failure of therapy or hypersensitivity to ZDV.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objectives and designBecause macrophages are the predominant immune cell and the predominant infected cell in the brains of patients with HIV encephalitis, we studied macrophage and immune activation-associated factors in the cerebrospinal fluid (CSF) from 39 autopsied AIDS cases for whom complete neuropathologic evaluation of the brain was available.ResultsCSF HIV p24 antigen was present in less than one-third of cases (11 out of 39). Less than half of the autopsies with moderate to severe parenchymal infection by HIV had high levels of CSF p24, although all autopsies with elevated levels of HIV p24 had moderate to severe HIV encephalitis. Elevated levels of cytokines, β2-microglobulin, neopterin, and quinolinic acid were observed.ConclusionsAlthough many of the CSF findings showed a strong correlation with each other, none showed a strong correlation with the severity of HIV infection of the brain itself. The absence of a close association between CSF abnormalities and HIV encephalitis could reflect the abundance of complicating opportunistic infections in these terminally ill patients or the inadequacy of CSF as a marker of basal ganglia involvement in HIV encephalitis. These findings complicate interpretation of clinical studies of CSF in patients with AIDS where neuropathologic evaluation is unavailable.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID