摘要:

ObjectiveTo estimate and compare the societal impact of HIV infection and AIDS with other selected causes of male mortality in terms of the indirect costs of future production lost.DesignDescriptive, population-based economic evaluation study.PatientsAll men aged 25–64 years for whom HIV/AIDS or another selected disease was listed as the underlying cause of death in Canada from 1987 to 1991, as reported to Statistics Canada.SettingCanada.Main outcome measuresPresent value of future earnings lost for men using a human capital approach based on potential years of life lost in men aged 25–64 years.ResultsAssuming a 2% annual growth in earnings and a 3% annual real discount rate, the present value of the total loss of future production for all men aged 25–64 years who died in Canada during 1987–1991 was estimated to be 39.74 billion 1990 US. Deaths due to HIV/AIDS accounted for 5.3% of this total loss or 2.11 billion in 1990 US$. Future production loss due to HIV/AIDS more than doubled during the period from 1987 to 1991, from 0.27 to 0.60 billion 1990 US$. The loss in future earnings attributable to HIV/AIDS was exceeded only by that of ischaemic heart disease (15.2%), suicide (9.4%), motor vehicle accidents (6.6%), and lung cancer (6.6%). In total, these five causes of death accounted for 43.1% of the total indirect cost of production lost for men aged 25–64 years during the 5-year period.ConclusionOur findings demonstrated HIV/AIDS mortality is already having a dramatic impact on future wealth production in Canada. If the past trend continues, the production lost in 1994 should exceed 0.86 billion 1990 US$ and will account for more than 10% of the total annual loss for men aged 25–64 years.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectivesTo analyze correlates of protection in macaques exposed to SIV.MethodsPeripheral blood mononuclear cells (PBMC) from macaques inoculated intrarectally with various dilutions of SIV were examined for theirin vitroproliferative response to SIV envelope peptides and generation of SIV-specific antibodies. Some macaques previously exposed intravenously to subinfectious doses of SIV were subsequently challenged 16 months later with an infectious intrarectal dose of SIV.ResultsThe viral-specific immune responses of macaques exposed to infectious doses of SIV were characterized by generation of antibodies and weak or undetectable T-cell-mediated responses. In contrast, macaques inoculated with doses of SIV below the threshold required for seroconversion and recovery of virus exhibited T-cell proliferation in response to SIV envelope synthetic peptides. The macaques that had previously been exposed to SIV resisted the subsequent virus challenge, whereas the naive macaques (never exposed to SIV) all became infected.ConclusionsThe inability to productively infect macaques previously exposed to subinfectious doses of SIV suggests that a T-cell-mediated response may confer long-term protection against infection, and that AIDS vaccines should be designed to optimize the cellular arm of the immune response.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectivesTo study the effects of microbial superantigens, Staphylococcal exotoxins (SE), on HIV replication in monocytes following binding to and signalling through major histocompatibility complex (MHC) class II molecules.MethodsWe investigated the effects of SE on HIV replication and monokine production in three differentin vitromodels of monocyte culture: chronically infected monocytic cell line U1, acute infection of normal monocytes by different HIV-1 strains, and naturally-infected monocytes from seropositive patients. p24 antigen, interleukin (IL)-6 and tumour necrosis factor (TNF)-α production was measured by specific enzyme-linked immunosorbent assay (ELISA).ResultsStaphylococcal enterotoxin B and toxic shock syndrome toxin-1 (1–1000 ng/ml) are powerful inducers of HIV-1 expression in U1 cells pretreated with granulocyte macrophage colony stimulating factor. SE induce viral replication in short-term cultures (days 6–21) of monocytes infectedin vitroby HIVBa-L, HIVLAI, or naturally infectedin vivo.Induction of HIV expression requires direct interactions of SE with MHC class II molecules but not T-cell receptor binding and T-cell-monocyte contact. Anti-TNF-α and anti-IL-6 neutralizing monoclonal antibodies inhibit by over 61% SE-induced HIV replication.ConclusionsUsing SE we have linked two important pathways for the regulation of HIV replication in monocytes, namely signalling through MHC class II molecules and monokine production potentially mediated by induction of the pleiotropic cellular transcription factor NF-B. In HIV-infected patients bacterial infections are common and could be an important cofactor in the immunopathogenesis of AIDS by inducing HIV replication in latently infected monocytes. Their prevention might emerge as beneficial in these patients.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveThe only two HIV-1 strains (ANT70 and MVP5180) reported to date from Cameroon are members of the outlier clade (group O). In this study, we assessed the prevalence of group O viruses and other HIV-1 subtypes in Cameroon.DesignA phylogenetic analysis of 18 HIV-1 strains isolated from seropositive individuals from Yaoundé and Douala, Cameroon.MethodsA 900 base-pair fragment of theenvgene coding for V3, V4, V5, and the beginning of gp41 of 17 out of 18 HIV-1 isolates from Cameroon was amplified, cloned and sequenced using polymerase chain reaction. A phylogenetic tree was constructed.ResultsThe overallenvnucleotide sequence divergence among the Cameroon isolates ranged from 6.1 to 27.5%. In a phylogenetic tree, six subtypes were identified when compared with 23 reference strains of different geographic origin. Of these 17 Cameroonian strains, 11 (61%) were of subtype A of which the interpatient distances at the sequence level varied from 6.1% to 18.3% (average, 11.9%). Three (17%) strains were of subtype F, and the other three strains (6% each) belonged to subtypes B, E and H, respectively. The remaining isolate was classified as belonging to group O, on the basis of the sequence of part of thepolgene. A very broad spectrum of different tetrameric amino-acid sequences was observed at the apex of the V3 loop. Eleven strains contained the tetrameric globally predominant GPGQ sequence at the tip of the V3 motif. Two strains had the GPGR sequence typical of the American and European HIV-1 strains. The remaining tetrameric sequences included GPGS, GSGQ, GRGQ, and GLGR.ConclusionThese findings on a limited number of viruses suggest extensiveenvgene diversity of HIV-1 strains from Cameroon, and could have implications for vaccine development in Africa.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo determine if the addition of recombinant (r) human interleukin (IL)-12 enhancesin vitroproliferative responses toMycobacterium aviumof peripheral blood mononuclear cells (PBMC) from HIV-positive donors with CD4 cell counts < 100 × 106/l.Design and methodsPBMC proliferative responses to virulent and avirulent serovars ofM. aviumin the presence and absence of exogenously added IL-12 were determined in 24 HIV-positive and 11 HIV-negative donors by3H-thymidine uptake assay. Changes in CD4 and CD8 cell populations after IL-12 treatment andM. aviumstimulation were analyzed by FACS.ResultsIL-12 significantly enhanced proliferation of PBMC to both virulent and avirulentM. aviumfrom all 24 HIV-positive donors (P= 0.0001) although the magnitude varied for each donor. In contrast, addition of IL-12 to PBMC from HIV-negative donors only increased the proliferative responses to the virulentM. aviumserovar 4 (P= 0.0044). PBMC from HIV-positive donors in the presence of IL-12 responded better to the avirulent serovar ofM. aviumthan the virulent serovar 4. Proliferative responses of HIV-positive donors toM. aviumalone, however, were significantly less (P= 0.0013) than that of HIV-negative donors. Increased proliferative responses of HIV-positive donors were independent of CD4 counts. No significant changes in the ratio of CD4+ to CD8+ T cells occurred in either HIV-positive or negative donors under any culture conditions.ConclusionIn vitroproliferative responses of PBMC from HIV-positive donors toM. aviumwere significantly enhanced by the addition of human rIL-12, which was not dependent on their CD4 cell counts. The use of IL-12 as an enhancer of cell-mediated immunity in AIDS patients againstM. aviuminfections deserves further study.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveWe compared the proviral DNA level in peripheral blood mononuclear cells (PBMC), viral RNA level in plasma, presence of p24 antigen in serum, viral phenotype, and results of immunological markers of HIV-1 disease.MethodsConsecutive samples of 62 HIV-1-infected patients, representing all stages of disease were tested for proviral DNA in PBMC and viral RNA in plasma using a semi-quantitative limiting dilution polymerase chain reaction (PCR). The presence of a syncytium-inducing (SI) phenotype was assessed after direct cocultivation of patient PBMC with MT-2 cells. Results of the quantitative PCR and the MT-2 coculture were correlated with the clinical stage of the disease, with the number of CD4+ T cells, and with the results of other virological and immunological markers, such as the level of p24 antigen, β2-microglobulin (β2M) and neopterin.ResultsSignificant differences were observed between the results for asymptomatic and symptomatic patients for all markers under study. In the group of asymptomatic patients with a CD4+T-cell count > 200 × 106/l, patients with high amounts of proviral DNA had significantly higher amounts of β2M, neopterin and viral RNA, they were more frequently p24 antigen-positive and harboured more frequently SI strains than patients with low amounts of proviral DNA. A good correlation between the proviral DNA and the viral RNA levels was observed. Significant changes of viral RNA but not proviral DNA levels were observed after initiation of therapy or when therapy failed.ConclusionsWe demonstrated the relationship between high proviral DNA level in PBMC, high viral load in plasma, elevated β2M and neopterin concentrations in serum, and the presence of p24 antigen in serum in a group of asymptomatic patients with a CD4+ T-cell count > 200 × 106/l. We suggest the possible usefulness of proviral load as an early indicator of disease progression. The presence of SI strains is highly correlated with disease; however, SI strains were detected in only 46% of symptomatic patients. It also appeared that the measurement of viral RNA levels is a useful marker for therapy monitoring.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo investigate the capacity of an HIV-1 immunogen to induce or augment HIV-1-specific delayed-type hypersensitivity (DTH) over a range of doses in asymptomatic HIV-1-seropositive adults.DesignA single center, double-blind, adjuvant-controlled, dose-ranging trial involving 48 HIV-1 -seropositive asymptomatic patients. Each dose group consisted of 12 subjects, eight receiving HIV-1 immunogen and four incomplete Freund's adjuvant (IFA). The doses studied were 50, 100, 200, or 400 μg (total protein). The HIV-1 immunogen was administered intramuscularly every 4 weeks for 36 weeks, with dosing contingent on the lack of an HIV-1 immunogen DTH response. A maximum of six doses was permitted.MethodsImmunogenicity was assessed every 4 weeks by DTH skin testing to the inactivated HIV-1 antigen in saline with >9 mm induration representing a response to immunization. Changes in p24-antibody levels were determined by endpoint titration using an enzyme-linked immunosorbent assay and Western blot.ResultsAt doses of > 100 μg, all treated patients demonstrated significant differences in the ability to mount an HIV-1-specific cell-mediated response relative to adjuvant controls. Dose-related response patterns were observed in the period between doses and the occurrence of rises in HIV-1 DTH. Treatment appeared to increase p24-antibody titers as well as reactivities to other HIV-1 antigens as determined by Western blots. The HIV-1 immunogen was well tolerated.ConclusionsThe minimum dose of the HIV-1 immunogen in IFA required to induce HIV-1 DTH relative to the IFA control group was 100 μg in this patient population.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo describe the clinical and radiographic presentation, risk factors, response to therapy and outcome of 16 patients with HIV infection and pulmonary infections caused byPseudomonas aeruginosa.DesignRetrospective review of medical records.SettingAn academic tertiary-care hospital.PatientsSixteen patients who met the case definition were included for retrospective review.ResultsP. aeruginosapneumonia was community-acquired in 15 patients (94%). The majority of patients (94%) had a diagnosis of AIDS with a mean CD4 cell count of 27 × 106/l cells. Traditional risk factors for the development ofP. aeruginosawere missing in most patients. Cavitary infiltrates were present on admission chest radiograph in eight patients (50%). An additional three patients (19%) presented with pulmonary infiltrates that cavitated subsequently. Clinical course was extremely varied with an in-hospital mortality of only 19%, but with an additional 25% of patients developing chronic or recurrent disease.ConclusionsCommunity-acquired pneumonia caused byP. aeruginosaoccurs in patients with end-stage HIV infection. The presence of cavitary pulmonary infiltrates on chest radiograph in a patient with a low CD4 count should raise suspicion ofP. aeruginosainfection. Obvious risk factors forP. aeruginosainfection may be absent. While the initial mortality rate is lower than that observed in other immunocompromised hosts, the potential for chronic or recurrent infection should be recognized and patients should be followed closely.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID