ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To determine the potential mechanisms for disease potentiation where feline immunodeficiency virus (FIV) infection of persistently feline leukemia virus (FeLV)-infected cats results in more severe FIV disease and increased mortality than FIV infection of specific pathogen-free cats.Design and methods:To determine whether pseudotype formation resulting in expanded cell tropism may be an important mechanism, cellular targets and tissue distribution of FIV and FeLV were determined byin situhybridization and/or immunohistochemistry. To determine whether FeLV can transactivate the FIV long terminal repeat (LTR) resulting in increased FIV expression,in vitrotransient expression assays were performed. To examine whether persistent FeLV infection can cause the deletion of a suppressive T-lymphocyte population, peripheral blood mononuclear cell (PBMC) cultures from persistently FeLV-infected cats were infected with FIV and monitored for FIV antigen levels.Results:Macrophages were the predominant target of FIV infection and were disseminated in a similar pattern in lymphoid and nonlymphoid tissues of both FIV-infected and FeLV/FIV-coinfected cats. FeLV-infected cells expressing FIV RNA were not present. Significant transactivation of the FIV LTR in FeLV-infected cells was not demonstrated. FIV antigen production was similar uponin vitroinfection of PBMC from FeLV-infected and uninfected cats.Conclusions:Neither direct virus/virus interactions, such as FeLV/FIV pseudotype formation or transactivation of the FIV LTR in FeLV-infected cells, nor deletion of a regulatory cell subset from the blood of FeLV-infected cats, was found to be the mechanism of disease potentiation.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To determine plasma cytokine levels [tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6] in African patients infected with HIV-2 relative to values in HIV-1-infected patients, and their relation to immunologic and clinical status.Design:Questions about the observed differences in the pathogenesis of HIV-2 and HIV-1 remain unanswered. Cytokines, especially TNF-α, are involved in the regulation of HIV-1 replication, and can be found in the plasma of HIV-1 -infected individuals. Therefore, we evaluated TNF-α, IL-1β and IL-6 levels in the plasma of African patients with different stages of HIV-2 disease. This was a 3-year prospective follow-up study.Methods:Cytokine plasma levels were assayed in 40 HIV-2− and 51 HIV-1 -infected patients from Africa. Nineteen of the 40 HIV-2-infected-patients underwent serial assays every 4 months for 3 years. Data were analysed in relation to the number of CD4+ and CD8+ cells, viral load and clinical status.Results:Plasma levels of TNF-α and IL-1β were significantly higher in all the HIV-1− and HIV-2-infected patients than in healthy controls; IL-6 levels were around the detection limit for all patients. TNF-α levels were lower in the HIV-2-infected than in the HIV-1-infected patients at all Centers for Disease Control and Prevention (CDC) disease stages, including the asymptomatic phase. The CD4+ cell count was always higher in the HIV-2-infected patients, regardless of CDC stage. The prospective follow-up showed that TNF-α levels remained stable during the course of HIV-2 disease, as did the CD4+ cell count and virus load.Conclusion:Lower and stable plasma TNF-a levels in African patients infected with HIV-2, associated with lower viral load and higher CD4+ cell count, suggests the existence of a more appropriate and efficient immune response to HIV-2 than to HIV-1.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To determine whether saliva could serve as an alternative to serum for HIV-antibody testing in an ongoing sentinel surveillance program in Thailand.Methods:Serum and saliva specimens were collected from 1955 individuals in four of the 73 sentinel sites of the national surveillance program in Thailand. Intravenous drug users, female prostitutes, and men attending sexually transmitted disease clinics were included as participants. All specimens were collected and tested anonymously. Saliva was gathered with the Omni-Sal collection device and analyzed for the presence of HIV antibodies using the immunoglobulin G antibody-capture enzyme-linked immunosorbent assay (GACELISA) laboratory test, specially designed for low concentration body fluids. Our gold standard was serum, collected and analyzed independently from the saliva specimens, using an ELISA test for screening and Western blot for confirmation. Linkage between serum and saliva was blind to the laboratory. A set of HIV-positive and HIV-negative quality assurance samples for both serum and saliva were also analyzed blind.Results:Findings are presented as observed in the field, and as quality assurance samples after the correction of various field and laboratory errors. The sensitivity of the GACELISA with saliva was 98.0% in the field (298 HIV-positive specimens), 100% after correction of errors (300 HIV-positive specimens), and 100% among the quality assurance samples (95 HIV-positive specimens). The specificity of the GACELISA was 99.4% in the field (1653 HIV-negative specimens), 99.6% after correction of errors (1654 HIV-negative specimens), and 100% among the quality assurance samples (96 HIV-negative specimens).Conclusion:Our findings support other published studies that also featured the GACELISA. We conclude that saliva is comparable to serum for assessing HIV antibodies in individuals for surveillance and screening purposes.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To validate the technique of HIV-1 culture from whole blood for the quantitation of viral load in infected children.Patients:Forty-three HIV-1-infected children were followed in two paediatric centres.Methods:Quantitative HIV-1 cultures from unfractionated whole blood using an end-point dilution technique were compared with simultaneous quantitative cultures of peripheral blood mononuclear cells (PBMC) and plasma.Results:Good sensitivity (93%) of the methods used was confirmed. A close correlation (r = 0.80) was observed between HIV-1 titres measured directly from whole blood and those expected from PBMC and plasma titres. The mean whole blood viral load was higher in patients with more severe signs of disease, but the difference did not reach statistical significance. The whole blood viral titres measured sequentially at monthly intervals remained within one dilution of each other in 16 of the 22 patients studied.Conclusion:In this study, the quantitation of HIV-1 in unfractionated blood allowed for a reliable and sensitive measurement of the whole blood viral load in infected children.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To determine whether the HIV-1 genomes that grow outin vitrofrom peripheral blood mononuclear cells (PBMC) better represent thein vivoquasispecies present in plasma or PBMC.Results:For one patient (9606), PBMC culture represented more accurately the plasma rather than thein vivoPBMC quasispecies distribution, because a large number of fat-defective proviruses present in PBMCin vivowere not detected in plasma nor in the PBMC cultures. For a second patient (9605), PBMC culture was representative of bothin vivoPBMC and plasmatatsequences, but selection of C2-V3envsequences was observed in PBMC cultures compared with sequences present in both plasma and PBMCin vivo.This selection consisted of the absence in vitro of genomes with certain amino-acid substitutions at or near conserved glycosylation sites of the C2 region at positions 276 and 289. Site 276 has been reported to be important for viral infectivity, and these substitutions may therefore have affected infectivity. In the third patient (10095), selection of bothtatand C2-V3 sequences was observed in culture as compared to plasma and PBMCin vivo.In contrast to the first two patients, this third patient contained V3 sequencesin vivothat were predicted to impart syncytium induction and enhanced replication capacity. It was these sequences that grew out preferentiallyin vitro.Conclusion:This study suggests that short-term PBMC culture is representative of HIV-1 genomes present in PBMC and plasmain vivoto the degree that they are infectious.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To provide background on five HIV-infected cohorts with documented seroconversion times and serum immunoglobulin (Ig) A and β2-microglobulin (β2M), CD4+ cell count and haemoglobin levels. To give a relative risks (RR) regression summary of the prognostic value of serial CD4+ cell count, IgA, β2M and haemoglobin measurements for clinical AIDS, and to examine whether cofactors such as current age, sex and exposure category affect these RR.Design:The Multicohort Analysis Project (MAP) workshop was an international collaboration which brought statisticians, immunologists and clinicians from the five cohorts to work together for 10 days. A predefined restricted database was made available by each cohort for the workshop.Setting:The Medical Research Council (MRC) Biostatistics Unit, Cambridge, UK hosted the MAP workshop from 19 to 30 April 1993.Subjects:MAP workshop database comprised 1744 patients with documented HIV seroconversion times, with 407 women, over 900 injecting drug users (IDU) and over 500 homosexual men; 363 patients had AIDS and there were 308 deaths.Main outcome measures:Descriptive statistics on survival and progression to clinical AIDS by cohort and exposure category, CD4+ cell count at AIDS diagnosis and pre-AIDS zidovudine therapy. RR summarizing the joint prognostic significance of serial markers and cofactors such as age, sex and exposure category for progression to clinical AIDS.Results:Slower progression to AIDS for IDU [95% confidence interval (CD, 0.35–0.71 ] and heterosexuals (95% Cl, 0.19–0.98) compared with homosexual men was confirmed after adjusting for current age-group and serial CD4+ cell counts. CD4+ cell counts at AIDS diagnosis were much higher among homosexual men before than after 1988 (median, 150 and 90×106/l, respectively). Little zidovudine use was observed among AIDS cases diagnosed before 1988 (2%) but increased use was recorded after 1988 and 1989 (24%) and even greater use after 1990 (59%). Low serial CD4+ cell count, haemoglobin levels and high serum IgA and β2M levels were associated with an increased risk of progression to AIDS. CD4+ cell count always provided prognostic information in addition to other markers; IgA and P2M (95% Cl, 1.23–1.50 and 105–1.51, respectively) were jointly prognostic. P2M did not provide significant extra information (95% Cl, 0.91–1.47) to the combination of serial CD4+ cell count and IgA, although haemoglobin did (95% Cl: 0.74–0.91 for 10g/l increase in haemoglobin). Interactions between cofactors, particularly exposure category and serial markers, were used to test for modifications in RR. The association between AIDS risk and serial CD4+ cell count was weaker, and with elevated IgA stronger, for homosexual men; RR associated with high β2M values were.lower for IDU, in whom β2M may be elevated for reasons other than HIV disease.Conclusions:IgA and β2M, which can be measured in small volumes of stored blood, are jointly predictive of progression to AIDS. Results were broadly consistent between cohorts representing different age-groups, seroconversion periods and exposure categories. Some regression effect modifications by exposure category were noted, however, which merit further independent study.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To investigate the usefulness of single determinations of serum immunoglobulin (Ig) A and β2-microglobulin (β2M) levels in estimating the time from HIV seroconversion.Subjects:Five cohorts were represented in the workshop. The Multicohort Analysis Project (MAP) workshop database comprised 1744 HIV-infected patients with documented HIV seroconversion times, 363 of whom had AIDS. Overall, 1430 patients had two or more pre-AIDS CD4+ cell counts (13056 counts); 896 patients had two or more pre-AIDS IgA measurements (6081 observations); but only 2964 β2M measurements were available.Main outcome measures:Marker paths for loge IgA and logeβ2M and for CD4+ cell count. Dependence on cofactors (age, sex, mode of HIV transmission) and attention to inter-individual variation in seroconversion level and annual decline in CD4+ cell count. Logistic discrimination was performed using cofactor-adjusted paired logeIgA and logeβ2M to date HIV infections as recent (within 3 years of seroconversion), intermediate, or distant (≥6 years after seroconversion). Transition intensities between immunologically defined states (using IgA or β2M) and to clinical AIDS.Results:Linear functional form described the decline in CD4+ cell count, except for the Italian cohort where a steeper annual loss of CD4+ cell count occurred in the first year than thereafter. CD4+ cell count at seroconversion depended on age and mode of transmission. Annual loss of CD4+ cell count was less severe in those infected by sexual transmission. Non-monotone functional form emerged for logeIgA with an initial decrease in the first year after seroconversion followed by an increase thereafter. LogeIgA levels were higher in older subjects and in those infected by sexual transmission, but lower in women. A quadratic growth curve described the marker path for logeβ2M, which increased for 5–6 years after seroconversion but declined thereafter. Logeβ2M values were significantly higher in older patients and injecting drug users, but lower in women. The considerable heterogeneity of marker paths between individuals affected all three markers, but marker values appeared to track within an individual. Discrimination based on paired IgA and β2M measurements from single blood samples performed poorly in classifying HIV infections as recent, intermediate or distant. High intensities of backward as well as forward transitions between immunologically defined states explained the poor discrimination based on single sample per individual.Conclusions:Further study of how serum IgA reflects HIV infection and careful clinical and statistical assessment of reduced β2M from 5 or 6 years after HIV infection are needed. The dependence of marker paths on mode of HIV transmission suggests that sexual transmission may have implications for HIV disease progression. The feasibility of using serum IgA and β2M, evaluable in single stored blood samples, to estimate time of HIV infection has been set back by our results.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:Primary prophylaxis againstPneumocystis cariniipneumonia (PCP) for patients with HIV infection has been recommended by the Centers for Disease Control and Prevention. We evaluated alternatives to routine primary PCP prophylaxis with aerosolized pentamidine.Methods:A total of 121 HIV-infected patients with CD4+ cell counts ≤ 200 × 106/l or an AIDS diagnosis were enrolled in a controlled study of aerosolized pentamidine as primary PCP prophylaxis. Patients were randomly assigned to treatment (n = 61) with aerosolized pentamidine once every month or to no treatment (n = 60). Patients were evaluated for PCP, mortality, morbidity and progression of HIV disease. Morbidity was estimated from the number of days patients were unable to work due to illness, number of days hospitalized and AIDS events.Results:Baseline characteristics were similar in the treatment and control groups and mean CD4+ cell counts were 116 and 107 × 106/l, respectively. Eight incidents of PCP and 19 deaths were observed in the treatment group during a median follow-up of 16.4 months (range, 2.3–32.4 months). Nineteen incidents of PCP and 13 deaths, of which one was related to an acute episode of PCP, were noted in the control group. Median follow-up of controls was 18.5 months (range, 3.1–32.9 months). Patients in the treatment group were unable to work 19% of the observation time and were hospitalized for 4.3% of that time. Corresponding figures were 20 and 3.0%, respectively, in the control group.Conclusions:Aerosolized pentamidine had significant prophylactic efficacy, but we could not detect any major effect on mortality and morbidity. The overall mortality and morbidity were not markedly influenced by PCP. Clinical check-ups and treatment of acute PCP could be a justifiable alternative to drug prophylaxis with aerosolized pentamidine in selected patients.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To assess pneumococcal and influenza vaccination coverage among HIV-infected adolescents and adults receiving medical care in the United States.Design:Periodic medical record reviews.Setting:More than 90 clinics, hospitals, and private medical practices in nine cities.Patients:HIV-infected individuals aged ≥13 years were included in the analyses of pneumococcal (n = 9737) and influenza (n = 6161) vaccination coverage.Main outcome measures:Documentation of receipt of pneumococcal and influenza vaccines in medical records during 6–18-month and 12-month periods, respectively.Results:Overall, 37 and 33% of individuals received pneumococcal and influenza vaccines, respectively. In general, vaccination levels varied little by age group, race/ethnicity, or mode of HIV exposure. Having had at least five medical visits was significantly associated with having received pneumococcal and influenza vaccines [adjusted odds ratio (OR), 1.7 for each]. Having a CD4+ T-lymphocyte count <200×106/l (adjusted OR, 0.8) and being female (adjusted OR, 0.7) were associated with non-receipt of pneumococcal vaccine. Lower pneumococcal vaccination coverage among women was mostly accounted for by pregnancy.Conclusion:Until new, more effective means of preventing pneumococcal disease and influenza become available, efforts should be directed towards improving vaccination levels among HIV-infected individuals.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID