ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To determine the relative frequencies of HIV‐1 p24 antigen and culture positivity in white and black patients.Design:Volunteers in the US military's HIV natural history study were 46% white, 44% black, 7% Hispanic and 3% other. Focusing on the comparable groups of whites and blacks, a retrospective analysis was performed of the results of virologic assays collected over a 2‐year period.Methods:p24 antigen was quantitated in sera with and without immune complex dissociation (ICD); viral isolation was performed by coculture of peripheral blood mononuclear cells.Results:Results of the two virologic assays were very similar in the two racial groups, both overall and after stratification by CD4 cell count. As reported previously, the concentration of serum immunoglobulin G was found to be greater in black than white subjects. In contrast to results with ICD, sera tested without ICD resulted in differing (higher) rates of antigenemia in whites than blacks (P= 0.002).Conclusions:The frequencies of p24 antigen and culture positivity were found to be independent of race. Previously observed racial differences in antigen positivity were likely to be due to more extensive antibody binding in blacks than in whites.AIDS 1995,9:325‐328

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objectives:To explore the possibility that HIV‐1 budding and cellular adhesion molecules co‐polarize at cell‐to‐cell contact sites. To investigate the incorporation of host‐cell‐derived adhesion molecules into HIV‐1.Methods:The cellular sites involved in HIV‐1 budding were examined by transmission electron microscopy. Single and double immunocytochemistry staining was used to evaluate the cellular distribution of the viral matrix protein and adhesion molecules. Quantitative flow cytometry was used to measure the cellular expression of adhesion molecules. An immunocapture technique was used to measure the presence of cell‐derived proteins on HIV‐1. The captured virus was measured by a p24 antigen assay. The infectivity of virus captured by monoclonal antibodies was tested by measuring the virus antigen yield in supernatants after the addition of sensitive cells.Results:Released and budding HIV‐1 was mainly localized at the cell‐to‐cell contact regions. This feature was consistent with a polarized staining for the virus matrix protein p18 at cell‐to‐cell contact regions. Intercellular adhesion molecules (ICAM)‐1 in HIV‐1‐infected cells were polarized on both isolated cells and syncytia, co‐localizing with HIV‐1 matrix protein. HIV‐1 incorporated all the adhesion molecules expressed by the host cells, although without quantitative correlation with their cellular expression.Conclusions:HIV‐1 is released at cell‐to‐cell membrane contact sites. Both ICAM‐1 and virus matrix protein co‐polarized on isolated cells and syncytia at the sites involved in the recruitment of uninfected cells. The impressive concentration of ICAM at cell sites where most virions are released may account for the acquisition of these membrane proteins by the HIV‐1 progeny, and may be important for the cell‐mediated spread.AIDS 1995,9:329‐335

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objectives:To investigate, in lymphocytes from HIV‐1‐infected individuals, the phenotypic expression of various adhesion co‐ or counter‐receptors [lymphocyte function‐associated antigen (LFA)‐3, LFA‐1 and intercellular adhesion molecule (ICAM)‐1] involved in providing the co‐stimulatory signal through the phospholipase C‐&ggr; pathway in relation to inositol polyphosphate metabolism.Design and methods:Cell adhesion molecule profiles of peripheral blood lymphocytes (PBL) from 39 HIV‐1‐infected individuals at various stages of infection and 20 healthy laboratory controls were studied using flow cytometry. These were studied in 14 patients with late‐stage disease in conjunction with their inositol polyphosphate metabolic profiles measured by high performance liquid chromatography. Levels of HIV‐1 present in cell lysates were concurrently measured by a p24 antigen capture assay. In addition, the effects of a specific anti‐ICAM‐1 antisense oligonucleotide on the intracellular phosphatase activities of lymphocytes from a separate group of eight HIV‐1‐infected individuals were examined.Results:The expression of LFA‐1, a &bgr;2 integrin, was upregulated among patient PBL in parallel with disease progression, whereas that of LFA‐3 (CD58) was found to be significantly reduced among the CD4+ lymphocyte subset in all stages of infection. The 5‐phosphatase activity, which we previously observed to be defective in HIV disease, was found to correlate linearly with the expression of both LFA‐1 and its ligand, ICAM‐1. Treatment of patient lymphocytes with an antisense oligonucleotide, which reduced the cell surface expression of ICAM‐1 by blocking the translation of its mRNA, resulted in further reduction of intracellular phosphatase activities.Conclusions:Our results suggest a pivotal role for adhesion co‐ and counter‐receptors in influencing lymphocyte signalling and hence cellular response to recall antigens in HIV‐1‐infected individuals.AIDS 1995,9:337‐343

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To characterize HIV‐1 quasispecies at high resolution to determine thein vivosequence heterogeneity of virus infecting the brain.Methods:A 1 kilobase region of the envelope gene, which includes the five hypervariable regions, was amplified by polymerase chain reaction (PCR) using DNA obtained from brain tissue of an HIV‐1‐infected patient. PCR products were cloned and 50 clones sequenced.Results:Thirty‐nine unique nucleotide sequences producing 35 protein variants were found. A consensus sequence was identified along with three distinct subtypes, each present at a level of 12%. The sequence variation from the concensus was 0.1‐2.1% at the nucleotide level with hypermutation and recombination responsible for the highest diversity. Sequence heterogeneity resulted in both the creation and the elimination of N‐linked glycosylation sites. Only nine clones differed from the consensus sequence in the V3 loop. No inactivating mutations were found.Conclusions:HIV‐1 proviruses found in the brain generally demonstrate a low level of genetic variability inenv.However, genomes that vary considerably from the predominant species can be present at significant levels. This observation may be of importance for understanding viral pathogenesis in the central nervous system.AIDS 1995,9:345‐349

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To determine the rate of development ofin vitroHIV resistance to (‐)2′‐deoxy‐3′‐thiacytidine (3TC) and relate the effect of dose to emergence of resistance.Methods:HIV‐infected men and non‐pregnant women, aged ≥ 18 years, with a CD4 count ≤ 300 × 106/l cells were fòllowed in a Phase I/II study, in which they were evaluated for tolerance to 3TC and effect of this agent with regard to viral susceptibility. Peripheral blood and plasma samples were collected at regular intervals for analysis. HIV was isolated using umbilical cord blood mononuclear cells as targets. These cells were also used in determinations of median inhibitory drug concentration. Specific amplification of the 184 mutation site, associated with HIV resistance to 3TC, was performed by polymerase chain reaction, using specific primer pairs, on DNA harvested from infected peripheral blood mononuclear cells (PBMC) of donors or, alternatively, on DNA that had been reverse transcribed from plasma‐associated HIV RNA.Results:Phenotypic resistance was detected in approximately one‐third of individuals studied, who were followed between 8 and 56 weeks. Development of 3TC resistance occurred independently of dose, although time of first appearance of resistant HIV‐1 variants appeared reduced at high 3TC doses. Amino‐acid changes at codon 184 in HIV‐1 reverse transcriptase were associated with, and preceded, the development of phenotypic 3TC resistance. Most commonly, a Met to Ile substitution appeared transiently before being superceded by a Val substitution at codon 184.Conclusions:In vitroresistance to 3TC developed in a high proportion of subjects who received prolonged monotherapy with this drug. The development of resistance to 3TC was associated with appearance of mutated viral forms and the disappearance of wild‐type virus, with regard to codon 184, in both patient plasma and PBMC.AIDS 1995,9:351‐357

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To estimate the prevalence ofin uterotransmission of HIV‐1 through the second trimester.Material and methods:One hundred consecutive, unselected, intact fetuses, beyond 15 weeks gestational age (mean, 22.4 weeks) were studied. These were obtained following spontaneous intrauterine deaths (n = 4), miscarriages (n = 4), and elective mid‐trimester terminations (n = 92), eight of which were fetuses with malformations from HIV‐1‐positive pregnancies. Coded DNA extracts from the fetal thymuses were tested blindly by polymerase chain reaction in three laboratories using a total of six different primer pairs.Results:Two thymuses tested positive [95% confidence interval (Cl), 0.2‐7]. Results from the three laboratories were consistent in all 100 cases. The two fetuses with HIV in the thymus both tested positive in other organs, demonstrating systemic HIV infection. The first fetus, whose mother had advanced AIDS, had diedin uteroand had diffuse toxoplasmosis. The second died following extremely premature delivery in a pregnancy complicated by repeated bleeding. HIV infection was observed in none of the 92 fetuses that resulted from elective mid‐trimester terminations (95% Cl, 0‐4).Conclusion:The frequency of earlyin uteroHIV infection appears to be low, compared with transmission rates in infants born to HIV‐1‐infected mothers, suggesting that transmission occurs mostly later in pregnancy and/or at delivery. Specific risk factors may have implications in the occurrence of early as opposed to late transmission.AIDS 1995,9:359‐366

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To determine whether a mucosal cytokine‐mediated inflammatory response is involved in cryptosporidial or microsporidial diarrhoea, as well as in diarrhoea of unknown origin in HIV‐infected patients.Design:Prospective study.Methods:Jejunal biopsies were obtained from HIV‐infected patients with diarrhoea. Controls were HIV‐infected and HIV‐seronegative patients without diarrhoea. Two biopsies were homogenized immediately and two other biopsies were first cultured for 20 h. Cytokines [tumour necrosis factor (TNF), interleukin (IL)‐1&bgr;, IL‐6, IL‐8, IL‐10], soluble TNF receptors (sTNFR) p55 and p75, and soluble IL‐2 receptor (sIL‐2R) were assessed in the homogenates and in the supernatants by sandwich enzyme‐linked immunosorbent or enzyme‐linked binding assays. The cytokine receptors were also measured in serum.Results:Six HIV‐infected patients with cryptosporidiosis, six with microsporidiosis, seven with diarrhoea of unknown origin, seven without diarrhoea, and seven HIV‐seronegative patients were eligible. Four patients were excluded because of the presence of other pathogens. No cytokines were detected in immediately homogenized jejunal tissue. Following culture, IL‐6 and IL‐8 levels were higher in HIV‐infected patients with diarrhoea of unknown origin than in HIV‐seronegative controls without diarrhoea, although this was not statistically significant. No differences in serum or post‐culture supernatant sTNFR p55 and p75 levels existed between the HIV‐infected patients with or without diarrhoea. sTNFR, IL‐1&bgr;, IL‐10 and the sIL‐2R were only detected in low amounts or not at all, and were equally distributed among all patient groups.Conclusions:This study indicates that mucosal cytokine‐mediated inflammatory responses do not play an important role in the pathogenesis of different types of diarrhoea in HIV‐infected patients. These results do not support the use of immunomodulatory therapy in these patients.AIDS 1995,9:367‐373

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To validate the World Health Organization/Global Programme on AIDS (GPA) protocol for measuring HIV/sexually transmitted disease prevention indicators pertaining to knowledge and sexual practices of the general population.Methods:Data were collected in Uganda during 1993. Three different interview strategies were complemented with qualitative methods, including observations at visits and key‐informant interviews. Two interview strategies consisted of structured questionnaires which were applied to 460 randomly selected people aged 15‐49 years and 60 intentionally selected women who were known prostitutes. The third strategy involved in‐depth interviewing and was applied to a random subset of all respondents (n = 75).Results:The three interview strategies generated similar results for demographic characteristics. The strategies using structured questionnaires gave similar results with regards to the number of reported sex partners and the prevalence of condom use, but differed from in‐depth interviews on these aspects. The high numbers of casual sex partners of female prostitutes was confirmed by in‐depth interviews but not via the questionnaires.Conclusion:The GPA questionnaire may not be optimal to capture people at high risk and to assess sexual behaviour, especially of people at high risk. Nevertheless, the questionnaire provides the most realistic option, since in‐depth interviews are expensive and not as objective in assessing trends over time. Evaluation studies of HIV interventions in the general population should therefore be complemented with small qualitative studies to detect and iron out biases in interpreting results.AIDS 1995,9:375‐382

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To identify the factors associated with the presentation of extrapulmonary tuberculosis (EPTB) in AIDS diagnosis and to analyse its temporal trend.Design:Analysis of AIDS surveillance data.Methods:The study was based on AIDS cases diagnosed in Spain between 1988 and 1993, and reported up to September 1994. The proportion of patients presenting with EPTB at AIDS diagnosis was analysed by sociodemographic characteristics and year of diagnosis.Results:Of the 22 445 AIDS cases diagnosed in Spain from 1988 to 1993, 6526 patients (29.1%; 95% confidence interval, 28.5‐29.7) presented with EPTB at diagnosis, making it the most frequent AIDS‐defining disease. The highest proportions of EPTB reported at AIDS diagnosis were observed for injecting drug users (IDU; 35.4%) and the heterosexual transmission category (23.5%). The proportion of EPTB was Iower in women [relative risk (RR), 0.85;P<0.001], and higher in 15‐29‐year‐olds (34.2%) and patients with a prison record (44.3 versus 25.4%; RR, 1.75;P<0.001). AIDS patients resident in provinces with high respiratory TB mortality rates among the general population exhibited a higher proportion of EPTB (RR, 1.45;P<0.001). The effect of any one variable was maintained by controlling for all others. The proportion of patients with EPTB at AIDS diagnosis revealed a downward trend from 1988 to 1993 (P=0.007), which was observed in IDU and heterosexuals but not in homosexual/bisexual men (P= 0.421).Conclusions:Factors such as injecting drug use, prison record or residence in high TB‐endemic areas are associated with a greater frequency of EPTB at AIDS diagnosis. These factors must be considered for specific prophylaxis to be efficiently applied.AIDS 1995,9:383‐388

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID