ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To evaluate the efficacy of immunopurified class I human histocompatibility leukocyte antigen (HLA) to protect against SIV infection.Methods:HLA class I antigens were immunopurified from a human B‐lymphoblastoid cell line. Groups of four macaques were vaccinated subcutaneously with four doses of the immunogen in adjuvant, or with adjuvant alone and subsequently challenged intravenously with 10 median monkey infectious doses of cell‐free SIVmac‐32H. Infection was determined by polymerase chain reaction for SIVmacproviral DNA and by virus isolation. Antigen‐specific humoral and cellular immune responses were monitored.Results:Macaques immunized with the HLA molecules produced anti‐HLA class I antibodies that inhibited SIV replicationin vitroand downregulated autologous T‐cell proliferation against irradiated C8166 cells. They were partially protected (two out of four) from virus infection for at least 33 weeks when challenged with SIV grown in human cells. All four control animals were infected.Conclusions:This demonstration of partial protection, together with our previous work reporting that vaccination with allogenic cynomolgus lymphocytes can protect against challenge infection with SIV grown in simian cells, suggests that allogenic immune response induced before or during establishment of HIV infection may have important implications for AIDS disease progression.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objectives:Expression of immunoglobulin (Ig) A Fc receptors (Fc&agr;R) and their saturation by endogenous lgA were studied on blood monocytes and neutrophils to evaluate the role of Fc&agr;R in the formation of increased serum levels of lgA and IgA‐immune complexes (IgA‐IC) observed during HIV‐1 infection.Methods:Peripheral blood samples were obtained from 45 patients at different stages of HIV‐1 infection and from 22 healthy volunteers. This study was performed using a quantitative flow cytometry method in which blood cells were stained with anti‐Fc&agr;R monoclonal antibodies (MAb) recognizing epitopes outside the IgA‐binding site and with F(ab')2fragments of anti‐IgA antibodies. Immunoprecipitations of radiolabelled surface Fc&agr;R molecules were analysed by sodium dodecylsulphate‐polyacrylamide gel electrophoresis under glycosylated and deglycosylated conditions.Results:This study reveals a diminished surface expression of Fc&agr;R on blood monocytes of HIV‐1‐infected patients, which follows disease progression. Fc&agr;R molecules on patients' neutrophils have a higher apparent molecular mass (60‐90kD) with normal protein core, suggesting expression of receptors with altered carbohydrate moieties. Increased levels of serum IgA significantly correlate with decreased levels of Fc&agr;R in HIV‐1‐infected patients. Surface Fc&agr;R molecules are saturated by endogenous IgA1 in both cell types.Conclusion:These findings suggest that defective expression and/or altered glycosylation of Fc&agr;R may result in receptor saturation, impairment of IgA catabolism and diminished clearance of IgA‐IC in HIV‐1‐infected patients. Fc&agr;R expression represents a new marker for disease progression.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:Maternal antibodies from either vaccinated or feline immunodeficiency virus (FIV)‐infected female cats (queens) were evaluated for their ability to protect kittens against homologous FIV infection.Design:Kittens that received different levels of maternal antiviral antibodies from either vaccinated or infected queens were inoculated with homologous FIV at 1 week post‐parturition and monitored for FIV infection. Maternal antiviral antibodies in the kittens were also measured and compared to the level of FIV infection.Methods:Kittens at 1 week post‐parturition were inoculated intraperitoneally with five median cat infectious doses of FIVPet. FIV infection was monitored by virus isolation for infectious FIV and by nested polymerase chain reaction for proviral DNA. Virus‐neutralizing (VN) antibodies and antibodies to FIV transmembrane peptide and core protein were also monitored throughout the 25 weeks.Results:Neonatal kittens that received high levels of antiviral antibodies from either vaccinated or infected queens were protected from FIV inoculation. Kittens that received low levels of maternal antiviral antibodies were not completely protected from similar FIV inoculation. Protection correlated more closely with the level of maternal VN antibodies than the anti‐p25 antibodies transferred to the kittens. The unprotected kittens born to infected queens were not infected from vertical transmission because all littermates that were not FIV‐inoculated remained free of FIV infection.Conclusions:Maternal antiviral antibodies, including VN antibodies, from either vaccinated or infected queens protected neonatal kittens from FIV inoculation. Thus, maternal antiviral antibodies play a key role in preventing or limiting infection in neonates and such antiviral immunity can be provided by vaccinated queens.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objectives:To develop a peptide‐based model for a preventive vaccine for HIV‐1 infection.Design:Phase I trial in HIV‐1‐seronegative volunteers.Participants:Adult healthy subjects HIV‐1‐antibody‐seronegative in an enzymelinked immunosorbent assay, screened for tuberculin [purified protein derivative (PPD)] reactivity with 2 tuberculin units PPD‐administered intradermally.Interventions:Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV‐1MN(PPD‐MN‐PND) were administered intradermally to tuberculin skin‐test‐positive and ‐negative volunteers.Results:Antibodies to the MN‐PND were measured after two immunizations in 10 out of 11 PPD skin‐test‐positive volunteers. After the fourth immunization high‐affinity antibodies were detected, which persisted for over 1 year. High titers of MN‐PND‐specific immunoglobulin (Ig) G and IgA were detected in the serum and saliva of all volunteers tested. Serum antibodies were cross‐reactive with PND peptide from some other HIV‐1 strains but neutralized only the HIV‐1MNprototype. Human leukocyte antigen (HLA)‐B7‐restricted MN‐PND‐specific cytotoxic T lymphocytes (CTL) were also detected.Conclusions:The PPD‐MN‐PND vaccine at submicrogram doses is safe and immunogenic in PPD skin‐test‐positive healthy adult volunteers. Long lasting humoral immune responses in the serum and saliva were possibly accompanied by HLA‐B7‐restricted CTL responses. This is a vaccine prototype that can be rapidly and inexpensively modified to include other peptide epitopes. It is especially suitable for use in a worldwide multibillion Bacillus Calmette‐Guérin (BCG)‐primed or tuberculosis‐exposed population at risk for HIV‐1 infection.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To study the predictive value of clinical criteria and polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) for the diagnosis of cytomegalovirus (CMV)‐related neurological disorders during AIDS.Setting:Four infectious diseases departments in two tertiary referral teaching hospitals in Paris, France.Design and participants:One‐year prospective study involving 164 consecutive immunosuppressed HIV‐seropositive patients undergoing lumbar puncture (LP).Methods:A tentative diagnostic classification, based on strict operational criteria and PCR assay of CSF, was performed at the time of LP. At the end of the study, tentative diagnoses and PCR results were blindly and independently compared with the firm diagnoses, based on central nervous system histology, clinical outcome and/or viral culture of CSF.Results:The tentative diagnosis showed CMV‐related neurological disease in 38 patients, and CMV DNA was detected in 42. Among the 88 patients for whom a firm diagnosis was possible, 26 had a diagnosis of CMV‐related neurological disease. The concordance between the tentative and firm diagnoses was 61%, with a kappa index of 0.40. In contrast, the sensitivity and specificity of PCR were respectively 92 and 94%, with positive and negative predictive values of 86 and 97%. The presence of CMV DNA in CSF was associated with an increased risk of death (P< 0.0001).Conclusions:Unlike clinical criteria, PCR detection of viral DNA in CSF can be used reliably for antemortem diagnosis of CMV‐related neurological disease, a frequent complication of AIDS in this study. This rapid method should make a major impact on the management of these patients.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To determine the impact of the introduction of clarithromycin and azithromycin on the treatment and survival of patients with AIDS and disseminatedMycobacterium aviumcomplex (DMAC).Design:Retrospective review over a 3.5‐year interval.Setting:Tertiary‐care, university teaching hospital.Patients:Charts of all patients with cultures of blood or bone‐marrow positive for acid‐fast bacilli (n = 103) were reviewed. Data on laboratory results at the time of DMAC diagnosis, antimycobacterial therapy, antiretroviral therapy, and survival was collected.Results:Prior to the availability of clarithromycin and azithromycin 61.5% of patients received antimycobacterial treatment compared with 92% afterwards (P= 0.0014). Median survival of treated patients was 255 versus 145 days for untreated patients (P< 0.001). Median survival of macrolide‐treated patients was 284 versus 168 days for patients receiving treatment without a macrolide (P= 0.09). Univariate predictors of survival were antimycobacterial treatment, use of antiretrovirals, and year of diagnosis. In a multivariate model, no antimycobacterial treatment (hazard ratio, 3.83;P= 0.003) was associated with shorter survival, and treatment without a macrolide (hazard ratio, 2.29;P= 0.075) showed a trend towards shorter survival versus treatment with macrolide‐containing regimens.Conclusions:The introduction of clarithromycin and azithromycin has been associated with an increase in the proportion of patients with DMAC receiving treatment and with increased survival of these patients.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To assess the operational aspects of isoniazid preventive chemotherapy (IPT) for tuberculosis in persons dually infected with HIV andMycobacterium tuberculosisidentified at an independent HIV voluntary counselling and testing centre in Kampala, Uganda.Design:HIV‐infected persons were counselled, had active tuberculosis excluded by medical examination, and were offered purified protein derivative (PPD) skin testing. PPD‐positive persons were offered isoniazid 300 mg daily for 6 months. Drugs were supplied, and toxicity and compliance were assessed monthly. Utilization of service, cost, and sustainability were also assessed.Results:Between 14 June 1991 and 30 September 1992, 9862 persons tested HIV‐positive. Of 5594 HIV‐infected clients who returned to collect test results, only 1524 (27%) were enrolled. Of those, 1344 were tuberculin‐tested (88%); 180 were not tested because of active tuberculosis, serious illnesses, refusal, and other reasons. Of the 1344, 250 (19%) did not return for test reading and 515 were negative (47% of tests read). Of 579 tuberculin‐positive persons, 59 (10%) were excluded from preventive chemotherapy because of tuberculosis and other respiratory illnesses. Of 520 persons given isoniazid, 62% collected at least 80% of their drug supplies. No major toxicity was observed. One case of tuberculosis occurred in the first month of treatment. Cost of HIV counselling and testing was US$ 18.54 per person and cost of follow‐up counselling and social support was US$ 7.89.Conclusions:Important factors were identified which caused attrition, such as limited motivation by counsellors to discuss tuberculosis issues during HIV pre‐ and post‐test counselling, insufficient availability of medical screening, shifting of sites to collect pills, and frequent tuberculin‐negative tests. Active tuberculosis among 6% of persons screened suggests that voluntary counselling and testing sites may be important for tuberculosis case finding and underscores the need to exclude tuberculosis carefully before starting IPT. In developing countries, further studies assessing the feasibility of IPT within tuberculosis and HIV/AIDS programme conditions are needed. Cost‐effectiveness of IPT, compared with passive case finding, and its sustainability should be assessed before national policies are established.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To assess the association between human leukocyte antigen (HLA) haplotypes and the incidence rates of CD4 decline to < 20% and to AIDS.Design:Retrospective cohort study of 95 HIV‐1‐infected hemophilic sibling pairs.Methods:HLA haplotype‐sharing between siblings was assigned on the basis of serologic typing of HLA class I alleles and molecular typing of HLA class II alleles. Concordance of time to CD4 decline to < 20% and to AIDS within and between sibling pairs was assessed by analysis of variance models and calculations of intraclass correlation coefficients. The age‐adjusted relative risks of these two endpoints for unique class II haplotypes were determined from proportional hazards models.Results:Sibling pairs sharing one or two haplotypes were significantly concordant in CD4 decline and AIDS status within 5 years of seroconversion. No concordance was found in pairs sharing zero haplotypes. At 6‐10 years after seroconversion, significant concordance of these two endpoints was also observed in the pairs sharing one haplotype. The concordant results were not explained by the use of zidovudine within the pairs. Among the individuals in this cohort, the relative hazards for CD4 decline to < 20% and for AIDS were significantly elevated for one class II haplotype (DQB1*0501, DQA1*0101, DRB1*0101). In addition, the risk for AIDS was significantly increased for two other class II haplotypes (DQB1*0603, DQA1*0103, DRB1*1300, DRB3*0202 and DQB1*0301, DQA1*0501, DRB1*1400, DRB3*0202) and significantly decreased for one haplotype (DQB1*0302, DQA1*0301, DRB1*0401, DRB4*0101).Conclusions:These data demonstrate that HIV‐1 disease progression is associated with the genes in the major histocompatibility complex that regulate the host's immune response.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To examine the relationship between income and AIDS rates in Los Angeles County (LAC) by race/ethnicity.Methods:1990 US census data were used to classify LAC postal zones (zip codes) by median household income into low‐, middle‐, and high‐income strata. AIDS rates were calculated for each income stratum based on 15805 AIDS cases diagnosed from 1987 through 1992 and reported to the county health department.Results:The AIDS rate was highest among residents of low‐income areas (252.8 per 100 000), intermediate among residents of middle‐income areas (161.2 per 100 000), and lowest among residents of high‐income areas (82.0 per 100 000). This trend in rates was present in all racial/ethnic groups examined and was most pronounced among whites (675.1, 226.7, and 88.4 per 100 000, respectively). Residents of low‐income areas accounted for 78% of AIDS cases among blacks, 67% among Hispanics, and 47% among whites.Conclusions:These findings suggest a strong inverse relationship between income and AIDS rates in LAC that is consistent across racial/ethnic groups. Prevention programs and treatment services should be directed most intensively to low‐income neighborhoods in this county.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID