摘要:

Summary:One of the functions of N-linked glycans of viral glycoproteins is protecting otherwise accessible neutralization epitopes of the viral envelope from neutralizing antibodies. The aim of the present study was to explore the possibility to obtain a more broadly neutralizing immune response by immunizing guinea pigs with gp160 depleted of three N-linked glycans in the CD4-binding domain by site-directed mutagenesis. Mutant and wild type gp160 were formulated into immunostimulating complexes and injected s.c. into guinea pigs. Both preparations induced high serum antibody response to native gp120 and V3 peptides. Both preparations also induced antibodies that bound equally well to the V3 loop or the CD4-binding region, as determined by a competitive enzyme-linked immunosorbent assay (ELISA). The sera from animals, immunized with mutated glycoprotein, did not neutralize nonrelated HIV strains better than did sera from animals, immunized with wild type glycoprotein. Instead, a pattern of preferred homologous neutralization was observed, i.e., sera from animals, immunized with mutant gp160, neutralized mutant virus better than wild type virus, and vice versa. These data indicated that elimination of the three N-linked glycans from gp160 resulted in an altered local antigenic conformation but did not uncover hidden neutralization epitopes, broadening the immune response.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:A potential component that may be useful for passive immunotherapy for HIV-1 is human monoclonal antibodies (HumAbs) possessing potent anti-HIV-1 activity that is directed against conserved regions of the envelope glycoprotein. Such antibodies would, in principle, have the ability to neutralize diverse isolates of HIV-1. To develop such reagents, hybridomas were derived by initial Epstein Barr virus transformation of peripheral blood mononuclear cells (PBMCs) from an asymptomatic HIV-1 seropositive donor followed by fusion with heteromyelomas, and secreted anti-HIV-1 antibodies were further characterized. The specificity of one HumAb, designated as clone 3, was determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses that indicated reactivity to the transmembrane envelope glycoprotein gp41. Synthetic pentadecapeptides overlapping by 10 amino acids were utilized for epitope mapping of clone 3; a decapeptide GCSGKLICTT in the transmembrane gp41 was identified as the epitope. Clone 3 bound to SupT1 cells infected with HTLV-IIIB in fluorescent activated cell sorting analysis. In addition, in vitro biological assays demonstrated that clone 3 possessed neutralization reactivity against diverse laboratory isolates as well as an AZT-resistant isolate. Therefore, clone 3 reactivity defines a conserved neutralizable site on the HIV-1 transmembrane glycoprotein. Clone 3 and the conserved immunogenic epitope on gp41 could be useful in passive and active immunotherapy for the acquired immunodeficiency syndrome (AIDS).

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The observation that the density of CD8+T-lymphocytes increases as the density of CD4+T-cells declines in adult HIV-1/AIDS patients, together with evidence that the total density of T-cells is regulated (homeostasis) has led to the suggestion that competition between lineages and classes of T-cells contributes to the pathology of HIV. We use a mathematical model of the interactions between populations of T-cells, HIV, and other parasites to explore the effects of T-cell homeostasis and competition on the progression to AIDS. We demonstrate that as a consequence of parasite-mediated T-cell replication, of competition within and between different T-cell clones, and random processes (T-cell drift), some CD4+lineages will be represented by relatively few cells,dearths,and some lineages may be lost, leavingholesin the immune repertoire. By killing CD4+T-lymphocytes, HIV accelerates the rate at which these dearths and holes accumulate and leads to an early breakdown of the immune control of HIV and other parasites, AIDS. When this model allows for intense, but not complete, competition between the CD4+and CD8+T-cell populations, it can account for most of the features of an HIV-1 infection in adults, including the gradual decline in CD4+T-cell densities and concomitant increase in HIV density, as well as the variability in time from infection to AIDS and the decline in the time from infection to AIDS in older patients.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:This study evaluated the efficacy of switching to didanosine in patients who were clinically or immunologically progressing despite zidovudine therapy. This multicenter, open-label study involved 400 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), who had tolerated zidovudine for at least 12 weeks and had signs of clinical or immunological disease progression. They were randomly assigned to receive 600 mg/d of zidovudine (n = 133), 500 mg/d of didanosine (n = 131), or 200 mg/d of didanosine (n = 136). The primary end point was a new AIDS-defining event or death. The study was prematurely terminated, after the first interim analysis, mainly owing to results of two controlled studies demonstrating that a change to didanosine was associated with an improved outcome in patients with advanced HIV-1 disease. The median duration of follow-up was 53 weeks. The primary end point rates were 41, 58, and 59 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups (zidovudine vs. didanosine 500 mg, relative risk 1.28, 95% confidence interval, 0.88-1.86, p = 0.19; didanosine 200 vs. 500 mg, relative risk 1.24, 95% confidence interval, 0.85-1.79, p = 0.26). In subjects with a baseline CD4 count of 100/mm3or more, the primary end point rates were 8, 29, and 25 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups, respectively (zidovudine vs. didanosine 500 mg, relative risk 2.96, 95% confidence interval 0.91-9.62, p = 0.07). No difference was seen in survival. In the didanosine 500 mg group, more patients had a 50% increase in CD4 cells (10% vs. 1% in zidovudine group, p = 0.01) and an increase of ≥2.5 kg in body weight (2% versus 3%). Fatal pancreatitis developed in one patient assigned to didanosine 500 mg and in one to zidovudine. Our data suggest that switching from zidovudine to currently recommended doses of didanosine in subjects with ARC or AIDS who show evidence of clinical and laboratory disease progression can be associated with improvements in clinical outcome as well as in surrogate markers of HIV disease progression. This effect tended to be greater among individuals with higher CD4 counts (>100/mm3).

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Adequate prenatal care has been linked to improved birth outcomes in general populations but has not been assessed in HIV-infected women. We examined longitudinal claims files and vital statistics records for women in the New York State Medicaid HIV/AIDS data base delivering a singleton from 1985 through 1990. Adequacy of the self-reported number of prenatal visits was assessed by the Kessner index. In logistics models, we estimated the association of prenatal care, illicit drug use, and other maternal characteristics with three outcomes: low birth weight, preterm birth, and small-for-gestational-age. Of 2,254 singletons delivered by this HIV-infected cohort, 28% were low birth weight, 23% were preterm birth, and 20% were small for gestational age. Two-thirds had inadequate prenatal care. Non-drug users had 57 and 26% lower adjusted odds of low birth weight and preterm delivery than drug users. The adjusted odds of low birth weight and preterm birth for women with an adequate number of prenatal visits were, respectively, 48 and 21% lower than for women with inadequate care. Adequate prenatal care was also associated with a 43% reduction in the odds of small-for-gestational-age. An adequate number of prenatal visits by women in this HIV cohort was associated with a significant reduction in all three adverse birth outcomes, but most had inadequate prenatal care. These data support strengthening efforts to bring pregnant, HIV-infected women into care.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The prognostic role of platelet (PLT) counts was evaluated in a cohort of 1,533 HIV-1-infected subjects followed for a median of 21 months. Thrombocytopenia (TCP), defined as a PLT count ≤100 × 109/L was present at enrollment in 11.2% of cases, with counts ≤50 × 109/L (severe TCP) in 5.3%. With the subject with normal PLT counts (PLT >150 × 109/L) as the reference group, the relative risk of developing acquired immunodeficiency syndrome (AIDS) was 0.8 [95% confidence interval (CI) 0.5-1.3, p = 0.4] for subjects with severe TCP, 2.1 (95% CI 1.4-3.1, p = 0.002) for those with PLT counts ranging from 51 to 100 × 109/L (moderate TCP), and 1.6 (95% CI 1.2-2.1, p = 0.0004) for those with borderline PLT values (PLT ranging from 101 to 150 × 109/L). Most of the risk increase associated with moderate TCP and borderline PLT values was explained by a higher prevalence of subjects with an older age and lower CD4+cell counts. However, at multivariable analysis considering age, sex, risk group, and zidovudine (ZDV) treatment, the risk for subjects with severe TCP remained significantly lower than that for subjects with moderate TCP and borderline values. These results suggest the existence of different types of HIV-1-associated TCP and also suggest that severe TCP (which often arises in the early phases of infection) is not related to disease progression.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The objective of this study was to determine whether granzyme B-expressing cells, which identify activated cytotoxic lymphocytes, are present in the small intestinal mucosa of human immunodeficiency virus (HIV)-infected patients with and without diarrhea. Therefore, duodenal biopsy specimens from 29 HIV-infected patients (11 with diarrhea and 18 without diarrhea) and 15 control patients were stained for the presence of granzyme B expressing cells. In HIV-infected patients, a significantly increased expression of granzyme B in the lamina propria was observed (p = 0.00001): In 22 of 29 patients, at least 5-10 cells per high-power field were counted. In contrast, in 13 of 15 control patients, granzyme B was not expressed or minimally so, and in two others a maximum of five granzyme-B-expressing cells could be detected per high-power field. No significant difference was found between the HIV-infected patients with and without diarrhea. Double staining revealed that the granzyme-B-expressing cells were mainly CD3 positive. These data show that activated cytotoxic T lymphocytes (CTLs) are present in the duodenal mucosa of HIV-infected patients. No relation between the number of CTLs and the presence of diarrhea was demonstrated. CTLs are known to be involved in the pathogenesis of HIV infection and in the production of tissue injury, but their functional role in intestinal HIV-related pathology has yet to be elucidated.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:We monitored trends in HIV risk behaviors and seroconversion among out-of-treatment injection drug users (IDUs) receiving street-based outreach intervention. Beginning in 1988, 641 HIV-seronegative IDUs were recruited by targeted sampling methods to reflect broader IDU populations and were followed for 4 years (1988-1992). All were active injectors not in treatment when recruited. Cohort members were targets of HIV-prevention outreach. The intervention was guided by the Indigenous Leader Outreach Model: Exaddicts deliver HIV-prevention services targeting IDU social networks in community settings. Primary outcome measures were HIV seroconversion and HIV risk behaviors. Observed incidence of HIV infection decreased, from 8.4 to 2.4 per 100 person-years. Prevalence of drug risk behaviors also decreased, from 100 to 14%. Seroconversion was associated with injection risk behavior [risk ratio (RR) = 9.8]. Sex risk behavior also decreased, but less dramatically, from 71 to 45%. Out-of-treatment IDUs in Chicago have reduced their rates of new HIV infection by reducing their injection risk behavior. New infections were strongly associated with injection risk behavior but not with sex risk behavior.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Would HIV-1-positive pregnant African women use interventions of AIDS testing, medication (oral or vaginal), and vaginal disinfection to reduce the likelihood of HIV-1 transmission to their child? In this pilot study in two west African cities (Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso), social workers gave a native-language questionnaire to 607 pregnant women at four Maternal and Child Health Centers. The women were asked about their perception of the HIV test; consequences of testing and counseling; choice of medical intervention to protect the future child; and feelings about being in a randomized, placebo-controlled, clinical trial. Most accepted the principle of an AIDS test, said they wanted the agreement of their regular partner before being tested, and would use interventions to reduce the risk of vertical transmission. The researchers concluded that although concepts of informed consent, randomization, and placebo are difficult to understand, the study results are promising and encourage the evaluation of clinical trials to reduce mother-to-child transmission of HIV-1 in Africa.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:To evaluate the demographic characteristics, risk factors, and reported mortality of adults and adolescents with AIDS and tuberculosis (TB), we analyzed surveillance reports of persons with AIDS from state, territorial, and local health departments. Of 72,306 persons with AIDS diagnosed in 1993, 3,589 (5%) were reported with TB; of these, 2,782 (78%) with pulmonary TB, 552 (15%) with extrapulmonary TB, and 255 (7%) with both pulmonary and extrapulmonary TB were reported. In multivariate analysis, black [odds ratio (OR) 3.3, 95% confidence interval (CI) 2.9-3.7] and Hispanic (OR 2.5, 95% CI 2.2-2.9) persons had a higher risk of TB than white persons; injecting drug users (IDUs: OR 2.3, 95% CI 2.0-2.5) and persons exposed to HIV by heterosexual contact (OR 1.4, 95% CI 1.2-1.7) had a higher risk than men who have sex with men, and persons who were foreign born (OR 2.1, 95% CI 1.8-2.4) had a higher risk than those born in the United States. The highest proportions of AIDS patients with TB were in New York (11%), Illinois (7%), Florida (6%), Georgia (6%), and Texas (5%). The 1-year mortality rate among AIDS patients with pulmonary TB only (26%) and among those with extrapulmonary TB only (28%) was lower than among those with other AID-defining illnesses (38%) (p < 0.001 and p < 0.001, respectively). The high rate of TB among persons with AIDS, particularly in specific areas of the country and HIV exposure groups, emphasizes the need for continued support of strong TB control measures among persons infected with HIV.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID