摘要:

SummaryAlthough laboratory-adapted strains of human immunodeficiency virus (HIV) are generally highly sensitive to neutralization by HIV-positive patient sera, we have found a more complex pattern of cross-neutralization and neutralization resistance among low-passage clinical isolates. These HIV isolates, like many other lentiviruses, resisted neutralization by the patient's own (autologous) antibodies. We assessed the degree of antigenic relatedness between different patient isolates of HIV through cross-neutralization with het-erologous sera and virus isolates. Complicated patterns emerged, with variation in breadth of neutralization among individual plasmas and variation in frequency of neutralization among isolates. In longitudinal studies of individuals, we found that some but not all such patients develop a neutralizing response that “catches up” with their earlier isolates after a lag period. Taken together, these data suggest that an individual's immune response broadens with time because of cumulative exposure to multiple antigenic variants that arise throughout HIV disease.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryStrong specific T-cell responses to human immunodeficiency virus type 1 (HIV-1) gp160 were induced by immunization with recombinant gp160 (rgp160). It was given as postinfection vaccination to 40 asymptomatic HIV-1 seropositive patients. The participants received 6 doses of 160 μg rgp160 administered intramuscularly at 0, 1, 4, 8, 17, and 26 weeks and were monitored for 1 year. Lymphocyte proliferation was performed by cultivating lymphoid cells in vitro with specific antigens and mitogens. After immunization with gp160, specific T-cell proliferative responses were induced in all 40 patients. One week after the sixth immunization at day 180, a substantially increased response was detected in 98% of the patients, with a mean stimulation index value of 195. Furthermore, proliferative responses were also identified, after immunization, against native gp120 and against a peptide representing the V3 region of gp120. In addition to the HIV-specific T-cell responses, increased reactivity to several other non-HIV antigens, including tetanus toxoid, influenza, measles, and cytomegalovirus, were seen after gp160 vaccination. The responses to CMV and measles were interpreted to represent an improved recall antigen response. Such recall antigen responses were few in matched HIV-infected controls immunized with influenza virus only. All patients initially and repeatedly showed a normal capacity of total T-cell activation, evaluated by the mitogen phytohemagglutinin (PHA). The trend in CD4 counts improved in 30 of 40 patients during the year of follow-up. The frequency of increases of proliferative responses to antigens was associated with a better CD4 trend. Addition of zidovudine for 2 weeks after each immunization had no beneficial effects nor did it prevent induction of immune responses. All patients tolerated the immunizations well, and no systemic adverse effects were noted. This is a phase I trial, and no definitive conclusions regarding clinical efficacy can be reached.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryLangerhans cells (LC) belong to the dendritic cell family and represent the principal antigen presenting cells populating squamous epithelia. We have reported the presence of human immunodeficiency virus Type 1 (HIV-1) proviral DNA and RNA in purified LC from the epidermis of seropositive patients. The aim of this study was to quantify HIV-1 proviral DNA in LC of infected patients using a competitive polymerase chain reaction (PCR) assay. Bulk epidermal cell (EC) suspensions were obtained from the skin of nine AIDS patients and six seronegative subjects. Purified LC and LC-depleted EC were prepared by immunomagnetic separation using an anti-CD la monoclonal antibody. LC preparations did not contain T cells, as assessed by reverse transcription PCR analysis of the T cell receptor β-chain gene (C region). In addition, no CD 14+cells could be detected in LC fractions by immunostaining of cytospin preparations. To quantify HIV-1 DNA, a new competitive PCR system was devised using SK145/150 as primers (gag) and a competitor plasmid DNA with a modified sequence (209 instead of 142 bp). The number of HIV-1 DNA copies found in the LC of AIDS patients ranged from 107 to 3,645/105LC. In contrast, LC-depleted EC from the same subjects were all negative. The results indicate that in AIDS patients the frequency of infected LC is comparable to that reported for peripheral blood CD4+T cells.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryHuman immunodeficiency virus (HIV)-induced destruction of follicular dendritic cells (FDCs), which are important in immunological memory, may be a major pathway of HIV pathogenesis. We use a mathematical model to investigate this hypothesis and conclude that a low level of FDC destruction could ultimately result in loss of control of HIV. Their slow turnover makes them good candidates for the part of the immune system that fails during the long period of HIV infection. As FDC destruction is essentially a misdirected immune response, too much immunotherapy may be detrimental. Our model shows how to estimate this critical level of immunotherapy. We derive an expression for the time taken to the loss of immune control. Transient changes in the viral growth rate before the immune system fails do not affect this time, providing a possible explanation for the results of the Concorde trial. We suggest that inducible B cell function is a good potential marker of disease progression, indicating the functional ability of the FDC network. Finally, we rereview data in the light of the FDC theory, paying particular attention to data on CD4+numbers and function that are inconsistent with the classical view of HIV pathogenesis.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryA progressive significant decrease of CD28 surface antigen expression on CD4+(mean, 90, 86, 79,68% in stages I, II, III, and IV, respectively, versus 96% in normals), as well as on CD8+T lymphocytes (mean, 38, 32, 31, and 29% in stages I, II, III, and IV, respectively, versus 47% in normals) was observed during HIV-1 infection. The increase of cytotoxic/suppressor T cells, in both percentage and absolute numbers, that was observed in almost all HIV-1 patients, was associated with an increase of the CD8+cells lacking the CD28 surface antigen. The loss of CD28 antigen expression was parallel to the increase of CD38, human leukocyte antigen (HLA)-DR, and CD45RO antigen expression on T lymphocytes throughout the disease. Furthermore, a positive significant correlation within the CD4+but not the CD8+subset was observed between the percentage of cells lacking the CD28 antigen and the percentage of cells expressing the HLA-DR and CD38 antigens, a finding suggesting that the loss of CD28 antigen expression on CD4+lymphocytes may be associated with T-lymphocyte activation. Patients treated with zidovudine showed no significant differences in the percentages of either CD4+CD28+or CD8+CD28+T-cell subsets when compared to untreated patients. These phenotypic changes may be associated with the functional defects of T lymphocytes in HIV-1 infected individuals.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryPersons with AIDS who have CD4+counts ≤100 and transplant patients, especially bone marrow allograft recipients, may experience clinically significant infections with acyclovir-resistant herpes simplex virus (HSV) or varicella-zoster virus (VZV). Patients who have received prior repeated acyclovir treatment appear to be at the highest risk of harboring acyclovir-resistant strains. Algorithms for the management of these infections were developed at a recent roundtable symposium. The consensus of the panelists was that treatment with foscarnet should be initiated within 7–10 days in patients suspected to have acyclovir-resistant HSV or VZV infections. Foscarnet therapy should be continued for at least 10 days or until lesions are completely healed. Recurrences may respond to either foscarnet or, occasionally, acyclovir.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryQuantitative serum antibody to p24 was evaluated as a predictor of risk of vertical transmission of human immunodeficiency virus type 1 (HIV-1) infection. HIV-positive mothers, 13 with HIV-infected children and 24 with noninfected children were investigated during pregnancy and at the time of delivery. A statistically significant difference in anti-p24 titers was found between the mothers with infected and those with noninfected children independent of whether antibodies were measured during pregnancy or at the time of delivery. High anti-p24 levels correlated with a low risk of vertical transmission, whereas low anti-p24 titers were associated with an increased risk of vertical transmission. Although the number of CD4+T-cells was lower and neopterin and beta-2 microglobulin values were higher in the group of mothers with infected children than in the noninfected group, no statistical significance was achieved due to the small sample size.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryWe analyzed matched cerebrospinal fluid and blood samples from 139 subjects enrolled in a study of the effects of human immunodeficiency virus type 1 (HIV-1) on the nervous system. Mean total intrathecal IgG synthesis rate was significantly higher in subjects with HIV-1-related neurologic disease (NeuroPos) than in HIV-1-seropositive (HIV +) subjects without neurologic disease (NeuroNeg) or at-risk seronegative controls (SNC). Mean trans-blood-brain barrier (BBB) albumin leakage (AL) rate increased significantly across groups (SNC < NeuroNeg < NeuroPos). AL was significantly higher in subjects with absolute CD4 counts <100/mm3versus those with <100 cells/mm3and significantly higher in AIDS compared with asymptomatic HIV +. Elevated total intrathecal IgG synthesis rate could not be accounted for solely by the presence of a damaged BBB, because 79% of subjects with elevated IgG synthesis rates had a normal BBB as assessed by the AL formula. Furthermore, the Tourtellotte formula inherently corrects for BBB leakage. We confirmed, using state-of-the-art albumin and IgG determinations, that intrathecal IgG synthesis is prevalent in all stages of HIV-1 disease. In the absence of a CNS opportunistic infection or tumor, mean total intrathecal IgG synthesis rate and trans-BBB AL are significantly higher in subjects with clinical HIV-1 CNS disease than in neurologically normally HIV + subjects.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryCentral venous catheters (CVC) are commonly used to deliver daily intravenous medications to patients with AIDS, and CVC-associated bacterial infections have been a cause of substantial morbidity in such patients. Although previous studies have reported rates of CVC-associated infections in AIDS patients, none has compared rates by type of intravenous drug regimen used or by whether CVCs were percutaneously placed or tunneled under the skin. The charts of all AIDS patients diagnosed with cytomegalovirus (CMV) end-organ disease at San Francisco General Hospital between 1985 and 1990 were reviewed for evidence of CVC use and CVC-associated infection. Infection rates and time to infection were analyzed for serious CVC-associated infections (requiring catheter removal or hospitalization for intravenous antibiotic therapy) by type of anti-CMV therapy administered (ganciclovir versus foscarnet) and by type of CVC (tunneled versus percutaneous placement). Fifty-four patients had 72 CVCs in use for 11,622 days of intravenous anti-CMV therapy. There were 36 CVC-associated infections of which 23 were categorized as serious (rate, 0.20/100 catheter days). In patients receiving either ganciclovir or foscarnet therapy, we found no significant difference in serious infection rates or in infection-free survival time (216 vs. 282 days, p = 0.7). However, serious CVC infection-free time was significantly longer in patients with tunneled than with percutaneous CVCs (419 vs. 195 days, p = 0.018). The use of ganciclovir compared to foscarnet in the treatment of AIDS-related CMV disease was not associated with a greater risk of serious catheter-related infection. However, a lower risk of serious CVC-associated infections was observed in patients with tunneled versus percutaneous CVC placement.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryWe studied human immunodeficiency virus type 1 (HIV-1) infection incidence over time in a 16-center cohort of hemophiliacs in the United States and Europe and estimated the most likely date of seroconversion for all seropositive subjects. Five U.S. centers enrolled subjects independent of HIV-1 status, whereas 11 centers preferentially included seropositive subjects. We obtained unbiased estimates of HIV-1 infection incidence rates from the five centers and estimated dates of seroconversion from the distribution seen among seropositives from all centers. In the five-center cohort, infection incidence began in 1978, peaked in October 1982 at 22 infections per 100 person-years at risk, and declined to 4 per 100 person-years by July 1984. Few infections occurred after 1987, and by that time, 50% of the cohort had become infected. Median seroconversion dates for subgroups of all seropositives ranged from July 1980 to December 1983, depending on the dose and type of factor concentrate. Median dates in Europe ranged from September 1981 to March 1983 and reflected the use of products manufactured from American plasma. Infection incidence apparently peaked about the same time that public health interventions were introduced to reduce transmission. These interventions, including heat treatment of factor concentrates and deferral of high-risk donors, have prevented HIV-1 infection from becoming endemic among younger birth cohorts of persons with hemophilia.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID