摘要:

SummaryTo quantify the number of human immunodeficiency virus type 1 (HIV-1) proviral copies per 1,000 CD4+cells in cerebrospinal fluid (CSF) and blood in relationship to stage of infection and HIV-1 neurologic disease (HND), 87 HIV-1 seropositive men without CNS opportunistic infections, tumors, or neurosyphilis, 9 high-risk, and 14 not-at-risk seronegative controls underwent a structured interview, and physical and neurologic examination followed by blood and CSF collection. A custom-designed, fully automated polymerase chain reaction (PCR) system performed amplification with use of two HIV-1gagprimer pairs, Southern blotting, and hybridization with product-specific probes. Image analysis was used to quantify band intensities relative to a dilution series. Eighty-one of 87 (93%) seropositive patients, 1 of 9 high-risk patients, (11%) and none of 14 seronegative controls had PCR-detectable HIV-1 in their blood. Fifty-seven of 63 (90%) seropositive patients, 2 of 5 (40%) high-risk seronegative patients, and none of 14 controls had HIV-1 in their CSF. The proviral load in seropositive patients, all stages, was significantly greater in CSF than blood [median 25 vs. 0.6 copies/1,000 CD4+cells (p = 0.0001)]. The median proviral load in blood was 0.09 copies/1,000 CD4+cells in seropositive, asymptomatic subjects, 10.7 in patients with AIDS, and 1.4 in patients with AIDS-related complex (p = 0.0281). CSF proviral load was greater in seropositive patients with HND than those without HND, median 43.5 vs. 17.6 copies/1,000 CD4+cells (p = 0.0614). Proviral load was greater in the blood and CSF of subjects with more advanced systemic disease and HND. There was a substantial penetration of HIV-1 into the CNS/CSF in both systemically and neurologically asymptomatic HIV-1 disease.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryTheenvgene of the human immunodeficiency virus-type 1 (HIV-1) was transfected in CEM-nkr, a human lymphoid cell line of T lineage that is resistant to the activity of natural killer cells, and for the first time, transfected T cell clones were established that stably express gp160 intracellularly and gp120 on the surface as demonstrated by radioimmunoprecipitation as well as by indirect membrane immunofluorescence. The regulatory protein vpu was not detected by radioimmunoprecipitation in these clones. The surface expression of gp120 without vpu in these clones provides direct evidence that gp160 is processed and cleaved (without vpu) in CD4+cells. The CD4 antigens of these cells coprecipitated gp160; interestingly, no reduction of the surface CD4 expression (detectable by flow cytometric analysis of membrane immunofluorescence with OKT4) in the transfected cells was observed. However, decreased reactivity of the transfected clones with OKT4A was observed. The gp120-expressing cells did not form syncytia on coculture with other CD4+human cell lines. These observations suggest the binding of gp120 to the surface CD4 antigen of the transfected cells. The transfected cells retained their resistance to the activity of the natural killer cells but showed a significant (p< 0.05) lysis when they were preincubated with AIDS patients' serum containing anti-gp120/41 antibodies. Thus, the expressed gp120/41 in these cells made them susceptible to killing by an antibody-dependent cellular cytotoxicity (ADCC) mechanism. To our knowledge, these are the first reported CD4+T cell lines that stably express HIV envelope proteins. These cell lines would be useful as targets in exploring gp 120/41-specific immune responses, especially in conducting gp120/41-specific ADCC studies in HIV-infected or gp120/ 41 (gp160)-vaccinated individuals.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryWe investigated the ability of human recombinant interleukin-7 (IL-7) to enhance the immune responses of mice vaccinated with either the alum-associated or liposome-formulated recombinant human immunodeficiency virus (HIV)-envelope protein, env-2–3SF2(a nonglycosylated denatured gp 120 of HIV-1SF2produced in genetically engineered yeast). Pathogen-free (C3H) mice were vaccinated on days 0, 14, and 28 with 10 μg of either the alum-associated env-2–3SF2 or liposome-formulated env-2–3SF2, both containing a lipophylic muramyl tripeptide, MTP-PE. Liposome-formulated IL-7 (5 μg/mouse) or empty liposomes were given on days 7, 14, 21, and 28. Antibody response against the immunized antigen, evaluated on day 21 and day 35 or 42, showed that liposome-formulated antigen induced higher antibody titer than did alum-associated antigen, and these antibody responses can be enhanced by concurrent administration of IL-7 liposomes. Spleen cells were harvested on day 21 and day 35 or 42 to evaluate cytotoxic T lymphocyte responses directed against autologous cells infected with vaccinia virus-expressing HIV-envelope protein. Mice treated with liposome-formulated antigen expressed the highest cytotoxic t-lymphocyte (CTL) activity, regardless of whether IL-7 liposome was given as an immune potentiator. In contrast, spleen cells from mice vaccinated with alum-associated antigen exhibited minimal CTL response, which was enhanced by concurrent IL-7 liposome treatment. Collectively, IL-7 liposome treatment enhanced the antibody production of the alum-associated or liposome-formulated env-2–3SF2, whereas its enhancement of CTL activity was detected only in mice vaccinated with alum-associated antigen.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryIt has been reported that HIV-1 p24 antigen (p24 Ag) detection is improved after dissociation of immune complexes using acid treatment (ICD assay). In order to evaluate the clinical significance of p24 Ag detected by the standard assay and by the ICD assay in pediatric patients, we related these measurements to clinical status, level of p24 antibody, and percentage of CD4+lymphocytes. Fifty-nine plasma specimens from 20 symptomatic HIV-1-infected children, collected prospectively over a 1-year period, were tested for these markers. Plasma was collected at the beginning of zidovudine therapy and ∼7 and 12 months thereafter. Compared with the standard assay, the ICD assay showed a higher number of samples positive for p24 Ag (78% versus 34%) and an increase in the levels of p24 Ag (median value of 129 versus 24 pg/ml). The anti-p24 antibody level was inversely correlated with the p24 Ag level measured by either assay. Four children negative for p24 Ag by both assays had a stable clinical course. In contrast, 50% of the children negative by the standard assay but positive for ICD p24 Ag and 75% of the children positive by both assays had progression of disease. No patients were positive by the standard assay but negative by the ICD assay. Children whose plasma tested positive by both assays had lower percentages of lymphocytes that were CD4+by comparison with children who were negative by both assays; children whose plasma tested positive only by the ICD assay formed an intermediate group. Antigen levels decreased in most of the p24 Ag-positive children during zidovudine therapy; however, those children whose levels increased or remained constant during therapy were more likely to suffer clinical deterioration. Our results suggest that the ICD assay may be useful as an indicator of disease progression but that better prognostic information is obtained by considering the results of both assays.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryIn response to recent laws regulating human immunodeficiency virus (HIV) antibody testing practices in all federal hospitals, our university-affiliated Veterans Affairs Hospital instituted several interventions designed to increase appropriate testing. Specific hospital policy requiring restriction of testing to high-risk individuals, provision of pre- and posttest counseling, and documentation of written consent was instituted. In addition, an education campaign to inform physicians of hospital policy and training of counselors as physician extenders was undertaken. To determine the efficacy of these interventions, we reviewed all HIV antibody tests performed during a subsequent six-month period (n = 221). Only 14% of tests met all hospital policy requirements. The decision to test was prompted by identification of a risk factor or other acceptable reason for testing for only 31% of patients. Risk reduction counseling was provided for only 28% of patients. Written consent was documented for 62% of patients. Health care providers on surgical services were less likely than others to comply with hospital policy (p < 0.0001). We conclude that an interventional program including specific hospital policy mandates, physician education, and provision of trained counselors was not adequate to ensure optimal HIV antibody testing practices. If this gap between policy and practice is to be closed, additional interventions, or alternatively modification of policy guidelines, will be needed.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryDuring a 7-year period, 32 patients withPseudomonas aeruginosainfection were identified on an HIV treatment service at a university-affiliated teaching hospital. The number of cases increased from 2 in 1986 to 13 in 1992. Affected patients had evidence of advanced HIV infection. In those treated with antiretroviral therapy, 96% of infections occurred > 1 year after initial presentation with HIV disease. Eighteen cases of pneumonia and 14 nonpulmonary (central venous access device, soft tissue, middle ear-mastoid, corneal, and peritoneal) infections were seen. Comparison with matched controls identified use of a central venous access device and administration of aerosolized pentamidine, corticosteroids, or ganciclovir as risk factors for infection (odds ratios, 5.3, 6.5, 15.0, and 9.0, respectively;p= 0.004, 0.007, 0.02, and 0.02, respectively). Seventy-five percent of cases had community onset, but time since last hospital discharge was significantly shorter in study patients than in controls (mean difference, −85 days; 95% confidence interval, −24 to - 146;p= 0.01). Among evaluable cases, outcome was fatal (survival ≈30 days) in 2 of 16 (13%) patients in whom initial antibiotic therapy was appropriate and 8 of 14 (57%) patients in whom initial therapy was not appropriate (p= 0.016). Ten recurrent infections were seen in 8 of 21 patients who survived the initial infection. Median survival after onset of infection was only 80 days.Pseudomonas aeruginosainfection is an increasingly frequent, severe complication of advanced HIV disease. Several treatment and prevention strategies used in the management of advanced HIV disease are associated with an increased risk of infection.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe variable rate of disease progression in HIV-1-infected patients treated with zidovudine may be related to certain viral characteristics, such as, antiviral drug resistance, virus burden, and viral syncytium-inducing (SI) capacity. Thirty-two HIV-1-infected patients treated with zidovudine (mean of 34 months) were studied to determine the relationship of SI phenotype and the codon 215polgene mutation (a marker of zidovudine resistance) to virus burden and CD4 cell decline. Patients with SI strains and the codon 215 mutation in their proviral DNA had a 54% decline in CD4 cells and a virus burden of 21,480 proviral DNA copies/106CD4 cells. In contrast, patients with non-SI (NSI) strains and wild-type at codon 215 had a 10% increase in CD4 cells and had a viral burden 1/46 that of patients with SI and the 215 mutation. Among patients with NSI strains, changes in CD4 cells depended on the presence of the codon 215 mutation (- 160 CD4 cells/μ), compared with those wild-type at codon 215 (+ 28 CD4 cells/μ1) (p< 0.01). There was a concordant rise in virus burden between proviral DNA and plasma HIV RNA depending on HIV phenotype and genotype. Using multiple linear regression, SI phenotype and the codon 215 mutation were found to independently predict CD4 cell decline and increased virus burden in zidovudine-treated patients.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryConcerns are sometimes expressed at the extent to which HIV-1 is prioritized within international and national health budgets and as a research issue, on the grounds that much larger numbers of people in developing countries currently die from other diseases, such as malaria and tuberculosis. We use a previously described mathematical model to explore how the HIV-1 epidemic could develop within a sub-Saharan African context and investigate the trends and patterns of adult mortality which could follow. Two contrasting scenarios are studied, one which turns population growth rates negative and another which does not. In both cases, HIV-1-related disease accounts for over 75% of annual deaths among men and women aged 15–60 years by year 25 of the epidemic. Relatively little change in mortality is seen in the early years of the simulated epidemics. However, by year 15, expectation of life at age 15 has fallen from 50 to below 30 years. The fragmentary evidence now available from empirical studies supports the impression that HIV-1 is rapidly emerging as a leading cause of adult deaths in areas of sub-Saharan Africa. Observed patterns of age-dependent mortality reflect those projected in the model simulations.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe significance of detection of human immunodeficiency virus (HIV) DNA by the polymerase chain reaction (PCR) in seronegative or sero-converting (SC) subjects remains controversial. In a previously reported study, we identified a case in which a specimen collected 12 months before serocon-version (pre-SC) was found repeatedly to be PCR positive in three experienced laboratories, while the 6-month pre-SC bleed was PCR-negative; PCR-based human leukocyte antigen (HLA)-DQA and -DRB typing of serial peripheral blood mononuclear cell (PBMC) samples from this case did not indicate a specimen mix-up or labeling error. To further investigate this case, we used HIVenvsequence and DNA heteroduplex gel-shift analyses to characterize HIV quasispecies present in serial pre- and post-SC specimens. HIVenvsequences and gel-shift pattern analyses from the 12-month pre-SC versus post-SC samples indicated that markedly distinct quasispecies were present, suggesting possible abortive infection followed by reinfection and subsequent seroconversion. However, the HIV burden of this pre-SC sample was very low (1 provirus/106PBMCs), and the quasispecies was highly heterogeneous, findings suggesting long-term rather than recent HIV infection. To test the hypothesis that the index pre-SC sample was PCR positive owing to trace blood contamination during initial processing, we analyzed the three seropositive samples collected on the same date in 1985. One of these samples was highly related to the index pre-SC sample byenvsequence and gel-shift methodologies. The source of contamination was further verified by PCR detection (using enhanced-sensitivity allele-specific primers) of HLA DR2 sequences unique to the contaminating source subject in the 12-month pre-SC PBMC sample from the index subject. This study shows that trace contamination during blood processing represents an additional basis for false-positive HIV PCR results and illustrates the usefulness of DNA heteroduplex gel-shift analysis and HLA allele-specific PCR in investigating such cases. NATIONAL GENBANK ACCESSION Numbers for these sequences: L20371 through L20380. inclusive.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThis article extends existing methods for estimating reporting delays to allow nonparametric estimation of how delays are changing over time. Also implemented are refinements to estimate calendar month effects and to improve the accuracy of trend estimates by focusing on delays of >6 months. Applying the method to 1987-definition adult and adolescent AIDS cases reported by June 1992 shows strong evidence for a nonlinear trend toward longer delays among cases diagnosed more recently and for slower reporting of cases diagnosed in January and June of each year. Combining estimated reporting delay corrections with the possibility of increasing underreporting produces a 14–16% higher estimated incidence by December 1991 and a 19–24% higher projected incidence by December 1993 than using the delay corrections provided with the public information AIDS data and assuming constant underreporting rates.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID