摘要:

Children born to HIV-1-positive mothers were prospectively tested for HIV-reactive IgG, IgM, and IgA by Western blot, in order to study the children's humoral immune response in the background of passively transferred maternal IgG. In infected infants, a response was first seen at 1–3 months forenv-reactive IgM and IgA, as well asgag-reactive IgM and IgG. This was followed by production of IgG toenv, IgA topoland togagp17 and p55 at 7–9 months, and IgG topolat 10–12 months. IgG Western blot positivity by all interpretation guidelines in all infected infants was found by 10–12 months. Subsequently, only IgG toenvand p24, and IgA toenvwere maintained in all, whereas IgG topoland p17 disappeared again in a significant fraction. A considerable proportion of uninfected infants also producedgag-reactive antibodies: IgM at 1–3 months, followed by IgG, which persisted in 10–20% and were also found in children born to uninfected mothers. These antibodies were, however, present at lower titers than in infected infants and were apparently produced in response to agent(s) different from HIV. Maternal antibodies toenvdisappeared significantly faster in infected than uninfected infants. Traces of HIV-reactive IgG were present for up to 21 months in children who subsequently seroreverted completely.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Antibody-dependent cellular cytotoxicity (ADCC) is an important antiviral effector mechanism. However, its role, as well as the functional integrity of the ADCC-effector cells in HIV infections, is not well understood. For studying gp120/41-specific ADCC, we recently developed a virus-free target cell system, using a natural killer (NK) cell activity-resistant human lymphoid cell line of B lineage, which was transfected with theenvgene of the human immunodeficiency virus type 1 (HIV-1); gp120/41-expressing cell clones were thus selected. In this study, these gp120/41-expressing cloned cells were used as targets in a gp120/41-specific ADCC assay for (a) examining the functional integrity of ADCC-effector cells from HIV-seropositive individuals, and (b) titrating the sera of these individuals for gp120/41-specific. ADCC-mediating antibodies. Our data indicate for the first time that the percentage of sera positive for ADCC-mediating antibodies to gp120/41 is higher in individuals with CD4 counts ±400 and ±200/mm3. The individuals with CD4 counts <200/mm3were found to have the lowest titers of these antibodies in their sera. The ADCC-effector function of the peripheral blood mononuclear cells (PBMC) of HIV-infected individuals was significantly (p< 0.05) reduced as compared to the PBMC from healthy, HIV-seronegative individuals. Further, human recombinant IL2 and interferon-γ were found to exert a significant (p< 0.05) enhancing effect on ADCC mediated by PBMC from these HIV-infected individuals. We also show that two virus neutralizing, gp120-specific mouse monoclonal antibodies 0.5β and 902 were unable to mediate ADCC as well as to block the ADCC mediated by the AIDS patients' sera. Further, these results suggest that the present gp120/41-expressing target cell system might prove very useful in conducting large-scale studies on both gp120/41-specific ADCC-effector function of peripheral blood mononuclear cells and ADCC-mediating antibody responses in different types of HIV-positive individuals.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

CD8+T cells from naturally infected disease-resistant sooty mangabeys (Cercocebus atys) secrete a soluble factor which inhibits the in vitro replication of the simian immunodeficiency virus (SIV). To gain further insight on the mechanism(s) involved. CD8+effector T cells and target cells from sooty mangabeys were immortalized and cloned. The target cells were then stably transfected with an SIV-LTR-CAT construct or with the parental CAT plasmid as a control. A quantitative RT-PCR method, providing the necessary sensitivity, was developed to monitor the influence of the cloned CD8+T cells on the CATmRNA contained in the target cells. It could be demonstrated that a soluble factor was secreted by the cloned CD8+T cells from sooty mangabeys, which appeared to regulate CATmRNA activity in a dose-dependent and reversible manner. Kinetic experiments showed that the CATmRNA transcriptional activity was initially augmented at 30 min postcoculture and was followed by a marked decrease in transcriptional activity after a few hours. This immediate early response could be mitigated utilizing H7, Calmodulin, or PDTC (a pyrrolidone derivative of dithiocarbamate), suggesting that the pathway was protein kinase-dependent and that the NF-B site may be involved. The inhibitory effect could also be overcome using a protein synthesis inhibitor, suggesting that protein synthesis was needed to negatively regulate CATmRNA activity and hence SIV promoter activity.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Cells obtained from the peripheral blood of HIV-infected patients and volunteers immunized with HIV-1 vaccines are commonly used to study anti-viral responses, since lymphocytes from the central lymphoid organs are difficult to obtain. Analyses involvingPBMCimplicitly assume that circulatingBcells provide an accurate reflection of the systemic humoral response induced by the HIV antigens. We examined this assumption by comparing the number ofBcells secreting IgG anti-gp160/120 antibodies in the peripheral circulation with serum antibody titers. Results indicate that neither the magnitude nor duration of the serologic response detected in HIV-infected patients or gp160/gp120-immunized volunteers reproducibly correlates with the number ofBcells secreting anti-envelope antibodies in the blood.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim–sulfamethoxazole (TMP–SMX) to prevent the first episode ofPneumocystis cariniipneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n= 214) with CD4 cell counts < 200/mm3or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP–SMX (400–80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP–SMX, respectively (p> 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP–SMX (p< 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP–SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP–SMX is less costly and should have a preventive effect for toxoplasmosis.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Neither single-agent therapy nor any combination treatment has been satisfactory enough to be regarded as standard in systemic advanced Kaposi sarcoma. In an attempt to achieve high efficacy in combination with low toxicity, we used a new liposomal formulation of doxorubicin. Pharmacologic data had established a long plasma half-life, an increased accumulation in tumor tissue, and a decrease in uptake by tissues such as liver, spleen, and bone marrow. In a phase I/II open-label, dose-escalating trial 40 male AIDS patients with advanced Kaposi sarcoma were enrolled to receive intravenous “stealth” liposomal doxorubicin biweekly at doses of 10 mg/m2(n = 10), 20 mg/m2(n = 27), and 40 mg/m2(n = 3). The median CD4 count at baseline was 25/μL. After six cycles (12 weeks), 39 patients were evaluable. Three patients (7.5%) showed a complete response, which was histologically confirmed. A partial response was documented in 33 patients (85%). Stable disease was observed in three patients (7.5%). During a median treatment duration of 25 weeks, four patients developed stomatitis (10%), and four patients (10%) experienced alopecia. The most frequent hematologic toxicity was neutropenia. Grade 4 neutropenia was seen in 42.5%, and grade 3 toxicity was seen in 30%. Toxicity was dose-dependent and more frequent in the 40 mg/m2stratum. During a median observation period of 25 weeks, opportunistic infections occurred in 57.5% of the patient population. We conclude that liposomal doxorubicin at dose levels of 10 and 20 mg/m2is safe and effective for treatment of advanced Kaposi sarcoma in AIDS. A controlled trial comparing liposomal doxorubin to conventional combination therapy is underway.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The aim of this study was to determine the contribution of injected-drug-use complications to the utilization of inpatient care by persons infected with human immunodeficiency virus (HIV). Retrospective chart review was done of all hospital admissions between January 1, 1991, and December 31, 1991, with outpatient records reviewed to establish CD4 counts within 3 months of the date of admission. The participants included 284 consecutive admissions (189 patients); admissions were divided into two groups according to the Center for Disease Control 1993 expanded AIDS definition: those with AIDS (CD4 count, <200 cells/μl) and those with early HIV disease (CD4 count, >200 cells/μl). Thirty percent of admissions occurred among persons with early HIV disease. Among 189 individuals admitted to the hospital, 84% were male, 62% were white, and 48% had injected drugs. Early HIV disease admissions were more likely to involve active injection-drug users (82% vs. 33%;p< 0.01). Admissions related to injected-drug use constituted 60% of early HIV disease hospitalizations, and this number rises to 72% if bacterial pneumonia is included as a substance abuse complication. Admissions related to injected-drug use constituted 27% of AIDS admissions: this number rises to 51% if bacterial pneumonia is included. Early HIV disease admissions were significantly shorter (9.9 vs. 12.6 days) and less expensive (mean charge, $9,592 vs. 12.873) than AIDS admissions but still accounted for 25% of inpatient HIV charges. Hospitalizations among HIV-infected persons early in the course of HIV disease are most often related to the medical complications of injected-drug use and account for a substantial expenditure of hospital resources. Early outpatient HIV care should focus not only on slowing the progression of HIV disease but also on limiting the morbidity of injected-drug use.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To evaluate the effect of recombinant human erythropoietin on anemia and health-related quality of life in patients with acquired immunodeficiency syndrome (AIDS), we initiated an observational study with an open-label multicenter treatment protocol that involved multiple academic and community physicians in the United States. Our subjects comprised 251 anemic (i.e., hematocrit < 30%) patients with a clinical diagnosis of AIDS using 1987 CDC criteria, age ≥ 12 years, and serum erythropoietin level ≤500 IU/L. The initial dosage of recombinant human erythropoietin was 4,000 units subcutaneously for 6 days each week. Based on the patient's response to therapy, the dosage was increased sequentially to 8,000 units subcutaneously for 6 days per week. Our measurements included changes in mean hematocrit and health-related quality of life. The interview included measures of energy/fatigue; physical, social, role and cognitive function: depression; health perceptions; and life satisfaction. Adverse experiences were also documented to assess safety. Changes in mean hematocrit level from a baseline of 27.9% to 33.6% at week 12 (p < .0001) and 34.5% at week 24 (p < .0001) were observed in patients treated with recombinant human erythropoietin. Adverse experiences, not clearly associated with AIDS, were reported by 10% of patients. Increases in energy (p < 05) were observed after 12 and 24 weeks of drug therapy, and increases in health perceptions were seen after 24 weeks (p < .05). No statistically significant increases or decreases were observed on measures of physical functioning, cognitive functioning, depression, social functioning, or home management activities over the 24-week follow-up. Anemia correctors (defined as hematocrit ≥38%) showed greater improvement in energy, health perceptions, home management, and role function than noncorrectors. Study dropouts and those who died had significantly worse scores for health-related quality of life at baseline compared to study completers. Thus, the AIDS patients with anemia and serum erythropoietin levels ≥500 IU/L treated with recombinant human erythropoietin showed increased mean hematocrit and improved health perceptions and energy levels. The drug therapy was associated with increased feelings of energy, but it was not associated with other changes in health status and well-being in the AIDS patients completing the study. These observations need to be confirmed in randomized clinical trials.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Using a national county database, we examine the hypothesis of increasing spread of acquired immune deficiency syndrome (AIDS) in rural America. Data for county-level AIDS caseloads for the period 1982–1990 were obtained by contacting state health officials of individual states. Yearly and cumulative AIDS cases by county or health district were converted to rates with use of the 1986 population figures. The data were grouped into 3-year periods, 1982–1984, 1985–1987, and 1988–1990, and analyzed. The top 25 counties that had the highest rates of increase were identified, and their average population sizes were derived. Pearson's correlation coefficients between the rates of increase and county populations were also computed. The results corroborate data from previous studies based on selected regions and clearly point to an increasing spread in rural counties on a national basis. During 1982–1984, highly populated counties had the highest rates of increase in number of cases of AIDS, with the populations of the top 25 counties averaging 1.1 million. Between 1988 and 1990, the top 25 counties that had the highest rates of increase are mostly rural counties with an average population of 73,000. Not only are we presently faced with a much larger base of population infected with AIDS than before, the epidemic has also entered a dangerous phase of spreading to rural America where health care facilities are far less adequate than in urban areas. Together with the recent sobering trends of spreading to the heterosexual population, low-income classes, and ethnic minority groups, the AIDS epidemic will have even more immense and far-reaching impacts on our society in the next decade.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID