ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo evaluate the immunological properties of a panel of human mucin MUC1/HIV V3 loop chimeras.DesignThe immunodominant epitope of MUC1 (APDTR) was found to be structurally isomorphous with the tip of the principle neutralizing determinant (PND) of HIV-1 (MN) (GPGRA). A panel of 120 residue, six tandem repeat (TR) and 60 residue, three TR chimeric antigens were constructed in which the repeating MUC1 epitope is replaced by HIV-1 PND. Each 20 residue TR contains one PND epitope. The PND of HIV-1 is presented in the native β-turn conformation at the crest of each repeating knob structure of the mucin-like protein.MethodsThe antigenicity of the chimeric antigens were compared using enzyme-linked immunosorbent assay (ELISA) and HIV-infected patient sera. Structural effects of antibody-antigen interactions were determined using surface plasmon resonance, with human monoclonal antibodies, chimeric antigens and the cyclic and linear V3 loops. Immunogenicity of three versus six TR was measured in mice.ResultsNine residues of the HIV PND substituted into the mucin backbone were equivalent to the 36 residue cyclic V3 loop in ELISA. The 120 residue antigens induced high liter, immunoglobulin (Ig) M and IgG, and HIV-specific antibodies in mice.ConclusionsMUC1/V3 chimeras efficiently detect HIV-specific antibodies in patient sera. Multivalent presentation of the PND is advantageous for higher affinity antibody-antigen interactions and for inducing HIV-specific IgM and IgG antibodies.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo compare hepatitis C virus (HCV) load in patients infected with HCV alone and those coinfected with HIV, and to evaluate the antibody response to HCV in the case of HIV infection.DesignPatients coinfected with both HCV and HIV have been shown to develop hepatic changes more rapidly, which may be due to an interaction between HCV and HIV. In a prospective study, serum samples were taken from 150 patients.MethodsUsing reverse transcription followed by polymerase chain reaction and the branched DNA assay, we detected HCV RNA in 75 patients coinfected with HIV and HCV and in 75 patients infected with HCV alone. The HIV RNA was also quantified by the branched DNA assay and the p24 antigenaemia was determined by enzyme-linked immunosorbent assay. The immune response to HCV was studied in the 150 patients by the use of third generation recombinant immunoblot assay (RIBA).ResultsAlthough a comparable number of patients had detectable HCV viraemia in both groups, HCV RNA was quantifiable in 79% of HIV-positive patients and in only 43% of HIV-negative patients (P< 10-5), and the mean HCV RNA level was much higher in the HIV-positive group than in the HIV-negative group (P< 10-7). The quantity of HCV RNA did not correlate with the CD4 count, p24 antigenaemia or HIV RNA level. The analysis of RIBA showed 14.7% indeterminate or negative results in the HIV-positive group and only 4% indeterminate results in the HIV-negative group. HIV-positive patients had reactivity to less antigen bands than HIV-negative patients (P < 10-3), and they had a weaker reactivity to c100, c33c and NS5 antigen bands than HIV-negative patients.ConclusionOur results show that in the case of HIV infection, the HCV RNA levels are strongly increased, but HCV load is not linked to the immunosuppression induced by HIV; therefore, the present data do not support the hypothesis of a direct interaction between HIV and HCV.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo determine the effects of rolipram, a specific type IV phosphodiesterase inhibitor, on tumor necrosis factor (TNF)-α production and HIV-1 replication.DesignTNF-α enhances HIV-1 replicationin vitro; blocking TNF-α and thereby inhibiting HIV-1 replication may therefore potentially delay progression of HIV disease. Pentoxifylline is a non-specific phosphodiesterase inhibitor that blocks TNF-α synthesis and HIV-1 replicationin vitroand has been shown in preliminary clinical studies to decrease viral replication in HIV-1-infected patients. Rolipram, which selectively inhibits the predominant phosphodiesterase isoenzyme of monocytes, inhibits lipopolysaccharide (LPS)-induced TNF-α with 500-fold greater potency than pentoxifylline. We, therefore, hypothesized that rolipram would be a powerful inhibitor of HIV-1 replication.MethodsThe effects of rolipram and pentoxifylline on TNF-α production and HIV-1 replication were determined in infected and uninfected peripheral blood mononuclear cells (PBMC), in a chronically infected promonocytic cell line (U1) and in an acutely infected monocytic cell line (BT4A3.5). TNF-α was determined by specific radioimmunoassay and HIV-1 replication was measured by p24 antigen and HIV-1 mRNA production.ResultsRolipram inhibited TNF-α production in LPS- and phorbol myristate acetate (PMA)-stimulated PBMC and in PMA-stimulated U1 cells. Rolipram also inhibited HIV-1 replication in the U1 cell line, as well as in acutely infected PBMC and BT4A3.5 cells. Depending on the experimental conditions, rolipram was 10–600 times more potent, on a molar basis, than pentoxifylline.ConclusionRolipram is a potent inhibitor HIV-1 replication and therefore deserves further investigation as a potential therapeutic agent in the treatment of HIV-1 -infected patients.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesTo describe the complete history of major opportunistic events experienced by 1883 HIV-infected persons prior to and specifically within 6 months of death, and to determine whether the frequency of specific events varies according to demographic characteristics, risk behaviors or geographic location.DesignDescriptive case series.MethodsOf 6682 HIV-infected individuals enrolled in studies sponsored by the Community Programs for Clinical Research on AIDS between September 1990 and June 1994, 1883 died during follow-up. A complete history of AIDS-defining events was determined for these patients by combining medical history data obtained at the time of enrollment, new events that occurred during follow-up, and causes of death.ResultsThe most common opportunistic AIDS-defining events these 1883 patients experienced before death werePneumocystis cariniipneumonia (PCP; 45%),Mycobacterium aviumcomplex (MAC; 25%), wasting syndrome (25%), bacterial pneumonia (24%), cytomegalovirus (CMV) disease (23%) and candidiasis (esophageal or pulmonary; 22%). In addition, 47% of patients experienced two or three AIDS-defining events before death, and 22% experienced four or more events. In the 6 months prior to death, 22% of patients had PCP, 21% had MAC, and 20% had CMV disease. Significant sex and ethnic differences were found: bacterial pneumonia occurred more often before death in women compared with men; fewer blacks and Latinos than whites experienced Kaposi's sarcoma (KS); and fewer blacks than whites had CMV disease before death. The percentage of patients with KS and CMV also varied by risk behavior. The frequency of 10 opportunistic diseases varied by geographic region after adjustment for demographic characteristics and risk behavior. Of note, many more patients in northeastern USA had tuberculosis and fewer had MAC.ConclusionA large percentage of individuals with HIV infection experienced multiple AIDS-defining opportunistic diseases before death. PCP, MAC, wasting syndrome, bacterial pneumonia, CMV disease, and candidiasis (esophageal or pulmonary) account for a substantial proportion of morbidity associated with HIV infection. More diseases varied by geographic location than by demographic characteristics or risk behavior of patients. Continued research on the etiology and prevention of these diseases and how they relate to one another should be a high priority.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease.Design and methodsA total of 966 homosexual participants in The Amsterdam Cohort Study were studied. Herpes zoster was defined by its characteristic clinical presentation. Incidence was calculated using Poisson regression, cumulative incidence by the Kaplan-Meier product-limit method and the prognostic value was evaluated using Cox proportional hazards model.ResultsThe incidence of first episodes of herpes zoster was 3.31 per 1000 person-years (PY) in HIV-seronegatives and 51.51 per 1000 PY in HIV-1-seropositive individuals. Recurrences only occurred in HIV-1-positive patients (25.6%). Cumulative incidences of first episodes increased linearly with the duration of follow-up. In HIV-1-seropositivesthe incidence was 31.2 per 1000 PY at CD4+ cells ≥; 500 × 106/l, 47.2 per 1000 PY [relative risk (RR), 1.51; 95% confidence interval (Cl), 0.78–2.94] at CD4+ cells 200–499 × 106/l and 97.5 per 1000 PY (RR, 3.13; 95%Cl, 1.54–6.32) at CD4+ cells < 200 × 106/l. Besides CD4+ cell counts, CD3 monoclonal antibodies and phytohaemagglutinin-induced T-cell reactivity were independent predictors for herpes zoster. The hazard ratio for AIDS after herpes zoster was 1.6 (95% Cl, 1.1–2.4) and for death 1.7 (95% Cl, 1.1–2.5), but these were not independent from CD4+ cell counts.ConclusionIn HIV-1 infection the incidence of herpes zoster increases with the decrease of CD4+ cell counts and T-cell reactivity, but herpes zoster is not an independent predictor for disease progression.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo evaluate the presence of endobronchial tuberculosis in HIV-infected patients.MethodsReview of the clinical records of HIV-infected patients in whom diagnostic bronchoscopy was performed because of pulmonary signs or symptoms during a 3-year period.ResultsSeventy bronchoscopies were performed in 59 HIV-infected patients. Tuberculosis was diagnosed in 25 patients, of whom six showed endobronchial tuberculosis. The most noteworthy radiological finding was mediastinal and/or hilar lymphadenopathy in five patients, occasionally associated with chest miliary infiltrates (in one), or a small pleural effusion (in two). Chest radiograph was normal in one case. The endoscopic findings were hyperaemia in five, caseating bronchial masses in four, or protrusion of extratracheal lymph nodes (broad, thickened carina and patchy bronchial lesions) in three out of the six patients.Mycobacterium tuberculosisinfection was confirmed by smear and culture from bronchial aspirate, bronchoalveolar lavage or bronchial biopsies. In three cases the diagnosis was confirmed by transcarinal needle mediastinal puncture aspiration. Tuberculosis was the first opportunistic pulmonary infection in every case. The clinical course with standard treatment was satisfactory in all cases with no bronchial sequelae.ConclusionEndobronchial tuberculosis may be more frequent than suspected in HIV-infected patients. Routine fibrobronchoscopy in HIV-positive patients with tuberculosis could show the true frequency of endobronchial tuberculosis.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo investigate the relation between HIV-induced brain lesions, zidovudine (ZDV) treatment and survival length in a well-defined population of HIV-positive patients.Methods and patientsUllevål Hospital has the responsibility for treating all AIDS patients from the city of Oslo except haemophiliac patients. The patient population in this autopsy study comprised all adult AIDS patients in Oslo who were treated at our hospital and died during 1983–1994 (n = 171). This represents 86% of all adult AIDS patients from Oslo who died during the same period. Full autopsy, including neuropathological examination of the brain and spinal cord, was performed on 128 (75%) of those who died.ResultsNo significant differences were found between autopsy and non-autopsy cases with regard to sex, age, risk groups, survival length or ZDV treatment. In the autopsy material, multinucleated giant cells (MGC) in brain tissue were found in 29 cases and diffuse damage of white matter in 52 cases. Analysis shows that ZDV (600 mg per day) reduced the incidence of these brain lesions, but only if continued until death. A second finding was an increased incidence of HIV-induced brain lesions for those with long-term survival. Together these observations may explain a substantial part of the time-trend in the incidence of MGC in Oslo. MGC were frequent (40%) during the first years of the epidemic, although survival length was short in this period. The incidence fell markedly around the time ZDV was introduced and later remained low in those using ZDV until death. The incidence of MGC has, however, increased during the later years, the new cases mainly occurring in patients who had discontinued ZDV use.ConclusionIf continued until death, ZDV can reduce the incidence of HIV-induced brain lesions in AIDS patients. When ZDV treatment is terminated a rapid increase occurs in the incidence of HIV encephalitis.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo provide basic information on pre- and extramarital sex in the general population and other factors related to HIV transmission.DesignCross-sectional household survey in 18 countries of the developing world, mainly in Africa and Asia.RespondentsRepresentative samples of 1300–6995 individuals aged 15–49 years,interviewed in 1989–1993.MethodsFace-to-face interviewing.ResultsWe observed a huge variability between study sites, with the proportion of men reporting sexual contact outside regular partnerships in the last year ranging from 4 to 47%. Contacts with sex workers range from 1 to 25%. Women were much less likely to report non-marital sex than men.ConclusionsThis first cross-cultural attempt to examine aspects of sexual lifestyles suggests that broad generalizations about multiple-partner sexual networking in particular regions are misleading. Gender, marital status, age and a few other demographic correlates were disclosed as powerful determinants of sexual behaviour, although the strength of associations varied greatly between specific locations. Condom use was very low in most study sites.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo describe the influence of pregnancy on immunological marker paths and progression of HIV-infected women.DesignAnalysis of prospectively collected immunological and clinical data collected on 145 women reviewed at the City Hospital, Edinburgh, between 1985 and 1992 using a two-level random-effects model that allows for within- and between-patient variance.ResultsThere were differences between the marker paths of women according to risk activity; women who had acquired HIV via injecting drug use (in addition to heterosexual intercourse) had a higher level of absolute CD4 cells, CD4% and total lymphocytes at seroconversion than those who had acquired HIV via heterosexual intercourse alone; however, immunological markers declined more steeply after seroconversion. There was no evidence that pregnancy, either before or after HIV seroconversion had an adverse effect on marker paths of HIV disease. There was a significant association between pregnancy after HIV seroconversion and post-pregnancy changes in immunological markers: an increase in the CD4% and a decrease in CD8%. However, causality cannot be implied as pregnancy itself may be associated with considerable lifestyle changes. During pregnancy the total white blood count rose due to an increase in the number of granulocytes, whereas the total lymphocyte numbers fell. The absolute CD4 lymphocyte subset counts fell progressively but the effect was due to the fall in the total lymphocyte counts, there being no influence of pregnancy on either CD4% or CD8%.ConclusionsIn asymptomatic HIV infection, changes in the absolute levels of CD4 and CD8 lymphocyte counts are primarily related to changes in the other components of the white cell count because there were no changes in CD4% and CD8%. Pregnancy itself has no adverse effect on immunological markers of HIV.

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID