ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo analyse the role of the apoptosis-inducing Fas receptor in the depletion of CD4+ and CD8+ T cells in HIV-infected individuals.MethodsPeripheral blood lymphocytes (PBL) obtained from HIV-infected subjects of all 1993 Centers for Disease Control and Prevention (CDC) stages and from non-infected controls were examined. A two-colour cytofluorometry was employed using monoclonal antibodies against Fas receptor (CD95) in combination with the surface markers CD4, CD8, CD28, CD26 and CD45RO. CD4+ and CD8+ T-cell-enriched PBL were used as target cells to assess their susceptibility to lysis by CD4+ cytotoxic T lymphocytes (CTL) which kill via the Fas pathway.Results: Fas+ PBL are more elevated in HIV-infected individuals than in HIV-negative controls and increase significantly from CDC stages A to C. Whereas Fas+CD4+ and Fas-CD4+ T-cell populations decline in parallel with the progression of HIV infection, the Fas+CD8+, but not of the Fas-CD8+ fraction, significantly increases. The Fas+CD8+ lymphocytes are susceptible to Fas-mediated lysis as they are efficiently killed by Fas-ligand+CD4+ CTL.ConclusionThe Fas receptor may contribute, but not as a unique cause, to the decline of CD4+ T cells in HIV-infected individuals. This and the significant increase of the number of Fas+CD8+ T cells indicates that Fas-mediated immune regulation is disturbed.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesWe investigated a selected group of 11 non-progressor, HIV-infected individuals 20 months prior to this study and found that they all had undetectable levels of viral RNA expression in their peripheral blood lymphocytes (PBL). Phorbol 12-myristate 13-acetate (PMA) and phytohaemagglutinin (PHA) stimulation of PBL produced easily detectable amounts of HIV RNA in only two out of five of these patients. Here we report the results of the virological and clinical follow-up of nine non-progressors from this group. We verified the stability of their non-progressive status and attempted to correlate it to specific virological markers.MethodsProviral DNA in lymphocytes was tested by semi-quantitative polymerase chain reaction (PCR). Detection of unspliced (US) and multiple spliced (MS) HIV RNA species in unstimulated and stimulated lymphocytes was performed by reverse transcriptase-PCR (RT-PCR). The amount of p24 antigen released into the media of lymphocyte cultures was measured using a standard procedure. Lymphocyte populations were depleted of CD8 cells by immunomagnetic purging.ResultsFollow-up of nine of these subjects showed that the patients who previously showed viral RNA activation following lymphocyte stimulationin vitro, developed a clinical and immunological progression characterized by CD4 count decline and lymphadenopathy. In contrast, all the other subjects maintained progression-free status throughout the follow-up period, with no detectable levels of HIV RNA in the PBL. Notably, this group of subjects showed no activation of viral RNA expression following stimulation of either undepleted or CD8-depleted lymphocytesin vitro.ConclusionThe group of non-progressors studied was found to be heterogeneous regarding the stability of the non-progressive status during the follow-up period. Our results suggest that the activation of HIV RNA expression following PMA-PHA treatment of lymphocytesin vitrois an early marker for future progression of the disease.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo analyse changes in cytokine productionin vitroand T-Iymphocyte immunophenotype in the early phases of HIV-1 infection.Design and methodsMitogen-stimulatedin vitroproduction of interferon (IFN)-γ, interleukin (IL)-2 (type 1 cytokines), IL-4, and IL-10 (type 2 cytokines) and surface expression of activation and non-activation markers were evaluated in 11 individuals HIV-infected for >3 but <12 months (seroconverters). The data were compared to those obtained in 33 asymptomatic HIV-positive individuals infected >3 years previously and who were stratified according to CD4+ lymphocyte count (group 1: >500 × 106/l, group 2: <500 × 106/l CD4 cells) and in 12 HIV-seronegative healthy controls.ResultsWe observed that the early phase of HIV infection is characterized by (1) reduced mitogen-stimulated IL-2 and IFN-γ production, (2) increased mitogen-stimulated IL-4 and IL-10 production, (3) a relative decrease in CD4+ and CD4+CD7− as well as an increase in CD4+CD7-CD57+ Iymphocytes, and (4) a relative increase in CD8+, CD8+CD38+ and CD8+CD57+ T lymphocytes. In addition, during a 6-month follow-up of six seroconverters we observed a dynamic pattern of changes of these parameters in most individuals, with a resulting profile similar to that observed in group 1 HIV-positive patients.ConclusionThe early phase of HIV infection is immunologically characterized by type 2 cytokine secretion and alterations in the expression of phenotypic markers, and closely resembles the more advanced phases of HIV infection. These immunologic alterations are temporally limited by the successive return to a more normal profile. Thus, HIV infection is an immunological complex dynamic process even in its earliest phases.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo study the development of the V3 region of the HIV-1 envelope over time, both within subjects and population-wide.MethodsDirect V3 sequences were obtained from viral RNA from seroconversion samples of 138 individuals [32 intravenous drug users (IVDU), 106 homosexual men], as well as from 5-year follow-up samples of 45 of these individuals (11 IVDU, 34 homosexual men).ResultsThe population-wide variation of the V3 region in both the seroconversion samples and the 5-year samples steadily increased over consecutive years and were of similar magnitude in each calendar year. The variation in the IVDU group was slightly lower (presumably lagging behind) than in the homosexual group, but also increased over time. The consensus sequence, representing the centre of the swarm of variants, remained almost stationary in 10 years of evolution. The V3 sequences from virions in serum collected 5 years after seroconversion still resembled those from the seroconversion sample, either in overall similarity or in specific (signature) amino acids. Seroconversion and late sequences from a donor-recipient pair were also very similar.ConclusionsThe variation in V3 sequences from seroconversion samples is as large as that in 5-year follow-up samples from the same calendar year, suggesting that there is no strong selection for a particular V3 genotype at transmission. The HIV-1 subtype B quasispecies in a naive population appears to evolve through unbiased expansion around a stationary consensus sequence. Despite its large variability, the V3 region retains many of its individual characteristics after 5 years of infection. This indicates that the sampling moment (relative to the seroconversion data) will not greatly influence the results of phylogenetic analyses.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo establish a robust procedure for the isolation and characterization of full-length expression-competent HIV-1 env genes directly from patient samples.DesignHIV exists as a quasispecies which can be disturbed byin vitroculture, in which numerous members of the population are likely to be defective due to the high error rate of the viral reverse transcriptase. Defective viruses are unlikely to play a dominant role in disease progression. Sinceenvgene translation products play major roles in the initiation and spread of infection we need to study genes with open reading frames.MethodsA nested polymerase chain reaction (PCR) approach has been used to rescue intact (2.6kb) env genes, which are cloned into a T7-promoter-containing vector. Expression of gp160 in CV-1 cells is detected by Western blot. Expression-competent clones are sequenced and resulting sequences used for phylogenetic studies. Translation products are analysed in relation to the known immunogenic structure of gp160.ResultsFrom random patient samples collected in London clinics, only HIV-1 subtype B was found. Two of the samples contained viruses with an additional pair of cysteine residues in their V1 regions. For samples collected in Uganda, HIV-1 subtypes A, D and an A/D recombinant were recovered.ConclusionAn effective procedure is described for the isolation of HIV-1envgenes directly from patient samples, which has worked for A, B and D subtypes to date. The PCR primers can be utilized with other subtypes with the possible exception of subtype O viruses. Phyiogenetic analyses revealed the potential importance of a G/C-rich region near thetat/revsplice site as a site of recombination. The sequences and translation products generated may be more relevant to disease progressionin vivoand vaccine formulations than those obtained from viruses selected in long-term culture.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo establish the syncytium-inducing (SI) phenotype and zidovudine (ZDV) susceptibility of HIV-1 isolates obtained from autopsy specimens.MethodsIsolation of HIV was attempted from autopsy specimens obtained from 76 AIDS patients. Specimens of Iymph node, spleen, spinal cord, brain and cerebrospinal fluid (CSF) were processed and cultured with peripheral blood mononuclear cells (PBMC) from seronegative donors. Biological phenotype was determined in a T-Iymphocyte line (MT-2). ZDV susceptibility was evaluated in a PBMC-based assay. Sequencing of amino-acid codons in the reverse transcriptase gene previously shown to be associated with ZDV resistance was carried out on a subgroup of isolates.ResultsHIV was recovered from tissue specimens and CSF up to 5 days post-mortem, but recovery rate of infectious virus decreased as the time between autopsy and specimen processing increased. There was a lack of concordance between PBMC isolates and isolates from different tissue sites with respect to SI phenotype. ZDV-resistant virus was isolated from post-mortem specimens of patients who had received long-term ZDV therapy up until or shortly before their death. ZDV-sensitive virus re-emerged in the Iymph node of patients who ceased treatment several months prior to death. Phenotypically sensitive virus obtained from Iymph node tissue of three patients after a relatively short time off ZDV (4–6 months) retained some of the amino-acid substitutions known to be associated with resistance.ConclusionThe data suggests that ZDV resistance and re-emergence of sensitive virus does not originate in peripheral cells, and that these cells and tissues are seeded with virus present elsewhere, possibly in the germinal centres of the lymph node.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo report 26 cases of acute retinal necrosis (ARN) in HIV-infected patients, to compare these data with the literature and to discuss the clinical spectrum of ARN during HIV infection.Design and settingTwenty-six HIV-infected patients with ARN, collected from five ophthalmology departments in Paris (France) between 1985 and 1993, were analysed retrospectively.PatientsTwenty-eight patients were enrolled; two were lost of follow-up. Diagnosis of ARN was established on the following criteria: (1) inflammation of the anterior segment and the characteristic triad, and (2) peripheral circular necrosis with centripetal progression toward the posterior pole associated with occlusive periarteritis and inflammation of the vitreous.ResultsARN is a late event in the course of immunosuppression (CD4+ Iymphocyte count <100 × 106/l). The most frequent presenting syndrome is a decrease of visual acuity, but signs related to a retrobulbar optic neuritis may also be present. In 60–90% of cases, vesicular viral eruption, usually shingles, precedes the onset of ARN by several days. Occasionally, neurological impairment is also present. Progression to blindness occurs in 76–85% of cases, bilaterally in 59%, and is usually induced by retinal detachment. This study and literature data suggest that varicella zoster virus (VZV) is directly implicated in the onset of ARN. At present, the most efficient therapeutic schedule is unknown.ConclusionARN is a rare and serious disease in AIDS patients. It is often associated with VZV infection. There is no preventive or curative efficient treatment. ARN might be considered as another opportunistic infection because of its rapid clinical evolution and severe prognosis.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesTo describe, in a retrospective study, the clinical and pathological spectrum of multicentric Castleman's disease (MCD) in HIV infection.PatientsThe diagnosis of MCD was established by lymph node biopsy in 20 HIV-infected patients. All patients had been HIV-infected by sexual contact. At diagnosis, HIV infection was asymptomatic in eight patients and Kaposi's sarcoma was present in 12. Mean±SD CD4+ cell count was 156 × 99 × 106/l.ResultsPatients were referred with a syndrome of fever and splenomegaly (100%), peripheral iymphadenopathy (90%), hepatomegaly (70%), severe weight loss (70%), respiratory symptoms (65%) and oedema (55%). Anaemia was a constant finding and seven (35%) patients presented with pancytopenia. Serum markers of inflammation were present in most patients: a high level of C reactive protein (90%), poiyclonal hypergammaglobulinaemia (89%) and hypoalbuminaemia (56%). The histological pattern of the lymph nodes was characterized by small hyalinized germinal centres surrounded by concentric layers of small lymphocytes, vascular hyperplasia, hyalinized vessels and large interfollicular sheets of plasma cells. Five patients were classified as plasma cell type MCD and 15 as hyaline vascular/plasma cell (mixed) type. Immunophenotyping studies (n = 1 3) demonstrated a poiyclonal B-cell process. No linkage with Epstein-Barr virus (EBV) could be demonstrated immunohistochemically using an anti-latent membrane protein-1 monoclonal antibody (n = 16) or by RNAin situhybridization with an EBV-encoded RNA transcript-specific probe (n = 1 3). Remission was obtained with low-dose and usually single agent chemotherapy in 16 patients. During follow-up, non-Hodgkin's lymphoma developed in two patients and Kaposi's sarcoma in three. Fatal outcome occurred in 14 patients with a median survival of 14 months.ConclusionMCD associated with HIV infection is a distinct clinico-pathological entity that can be differentiated from other types of HIV-associated systemic lymphoproliferative disorders. It is very similar to MCD observed in non-HIV-infected patients, except for the high prevalence of pulmonary symptoms and for the stronger association with Kaposi's sarcoma. Single-agent chemotherapy with vinblastine is effective and may prolong survival.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo identify factors associated with failure to return for HIV post-test counselling in pregnant women in Kigali (Rwanda).Subjects and methodsIn the context of a study on the impact of HIV infection on pregnancy, HIV-1 -antibody testing was offered to all pregnant women attending the antenatal clinic of the Centre Hospitalier de Kigali from July 1992 to August 1993. Pre-test counselling was performed after verbal informed consent was obtained. Two weeks later, we formally enrolled all HIV-positive women and a corresponding number of HIV-negative women in a cohort. At this visit, post-test counselling was given to those wishing to be informed of their HIV serostatus. Level of knowledge about modes of HIV transmission and condom use were recorded. Four months after delivery, another interview was conducted to determine the proportion of women who used condoms regularly.ResultsA total of 1233 pregnant women were screened. The HIV seroprevalence was 34.4% [95% confidence interval (CD, 31.7–37.1]; 271 (63.9%) out of 424 HIV-positive and 577 (71.3%) out of 809 HIV-negative women asked for their HIV serostatus (P= 0.008). In multivariate analysis, the only variable significantly associated with failure to return for post-test counselling was a positive HIV test result (odds ratio, 0.7; 95% CI, 0.5–0.9;P= 0.009), independently of obstetrical history and socioeconomic characteristics. Among the 848 women who had post-test counselling, 50.9% of the HIV-positive women and 94.6% of the HIV-negative women stated that they planned to inform their partner of their serostatus (P= 0.0001). More than 95% of the women interviewed knew about sexual and parenteral transmission of HIV, but half were unaware of mother-to-child transmission. More than 80% of the women had seen a condom before, but 14% only had used it at least once. Among women who were sexually active 4 months after delivery, 8.8% of the HIV-positive and 3.9% of the HIV-negative women reported using a condom (P=0.04).ConclusionInnovative approaches for HIV testing and counselling programs are needed and the importance of psychosocial and cultural factors associated with HIV testing should be emphasized in African populations.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID