ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveRetroviruses can activate the complement system in the absence of antibodies, and the purpose of this study was to examine whether the serum collectin, mannan-binding protein (MBP), could mediate such complement activation.DesignVirus envelope proteins gp120 and gp110 from HIV-1 and HIV-2 were incubated in microtitre wells coated with anti-gp120 or anti-gp110 antibodies. After further incubation with serum, complement activation was measured as deposition of complement factor C4 and C3 onto the wells. Deposited C4 and C3 were detected with enzyme-labelled antibodies. Normal human serum depleted of endogenous lectins by affinity chromatography was used as the complement source. Serum from C1q-deficient patients was used in some experiments. Complement activation was then assessed with and without prior addition of MBP to the wells. Complement activation was also correlated with the quantity of endogenous MBP in a number of normal sera.ResultsComplement activation by HIV envelope glycoproteins was found to be mediated by the binding of MBP to carbohydrates on natural envelope protein produced in virus-infected cells, as well as on glycosylated recombinant envelope proteins produced in insect cells. Non-glycosylated recombinant envelope proteins produced in Escherichia coli did not induce this type of complement activation.ConclusionsActivation of the classical complement pathway by retrovirus envelope proteins can be initiated by the binding of MBP to carbohydrate side chains of envelope glycoproteins.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo evaluate the immune response to HIV-1 p24 generated in vivo by p17/p24:Ty virus-like particles (p17/p24:Ty-VLP) by examining the lymphoproliferative and antibody (Ab) responses to HIV-1 p24, as well as Gag-specific cytotoxic T lymphocytes (CTL), in HIV-seronegative volunteers immunized with hybrid p17/p24:Ty-VLP.Design and methodsSixteen HIV-seronegative volunteers were immunized with p17/p24:Ty-VLP at two dose levels (100 or 500$mU.g) and monitored for the following 48 weeks for production of anti-p24 and anti-p17 Ab, in vitro lymphoproliferative responses to HIV-1 p24 and p17, and in vitro CTL responses to HIV-1 Gag.ResultsTwelve out of the 16 volunteers had significant p24-specific proliferative responses, with volunteers on the higher dose schedule exhibiting earlier proliferative responses than those on the lower dose schedule. Proliferative responses in both volunteer groups were similar in overall magnitude but appeared at different times during the immunization schedule. Anti-p24 Ab were detected in six out of the nine individuals in the lower dose group and in five out of the seven in the higher dose group. There was a good correlation between the presence of p24-specific Ab and the detection of lymphoproliferative responses to the p24 protein in peripheral blood mononuclear cells isolated from the same individuals. Anti-p17 Ab were detected in five volunteers. No Gag-specific CTL responses were detected.ConclusionWe conclude that hybrid HIV-1 p17/p24:Ty-VLP are capable of inducing both cellular and humoral immunity to HIV-1 Gag p17 and p24 components and are worthy of further study as a potential HIV immunotherapeutic.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo evaluate the decline in CD4+ counts in relation to the incidence of AIDS in different cohorts of homosexual men and to quantify possible consequences of laboratory variation in CD4+ measurement.MethodsOur study includes 403 men with well documented dates of HIV seroconversion originating from five cohort studies among homosexual men. Differences in time from HIV seroconversion to the first CD4+ count dropping <500 or 200 $$ 106/l and to AIDS were evaluated using Kaplan-Meier survival analyses.ResultsWe found considerable differences between cohorts in CD4+ depletion, but not in the incidence of AIDS (1987 definition).ConclusionsVariation in CD4+ depletion appears to be mainly the result of laboratory differences. Policy recommendations on a basis of CD4+ counts probably requires a calibration of measurement. The 1993 AIDS case definition leads to a site-specific shortening of the incubation time, which complicates the study of the natural history of HIV infection and of trends in the AIDS epidemic.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo evaluate an acid pretreatment method designed to dissociate HIV p24 antigen from immune complexes in serum.DesignPatient sera and sera containing experimental immune complexes were quantified for p24 antigen before and after immune complex dissociation (ICD). The clinical application of ICD was assessed in 1328 serum and plasma samples collected from HIV-infected patients.MethodsImmune complexes were created artificially by mixing purified p24 antigen with antibody-positive sera or a standardized concentration of human antibody to p24. ICD was achieved by incubation of samples with an equal volume of Clycine HCI for 90min at 37$$C followed by neutralization with Tris NaOH. Samples were quantified for p24 antigen using a commercial enzyme-linked immunosorbent assay (ELISA) kit.ResultsICD resulted in significant release of purified antigen from simulated immune complexes in antibody-positive sera. Variation in antigen sequestration and dissociation was related to anti-gag antibody titers. ICD resulted in complete recovery of 500 pg of antigen complexed with human anti-p24 antibody at concentrations up to 2.5 U/ml. In seropositive patients, the mean level of serum antigen was 3.5-fold higher after ICD, and an additional 21% were antigen-positive.ConclusionsPretreatment greatly improved antigen detection in HIV-antibody-positive sera by effectively dissociating immune complexes without compromising reactivity of the antigen itself. The treatment also facilitated routine monitoring of patients by revealing fluctuations in serum antigen that were indistinguishable or poorly defined in untreated sera.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo assess whether oral acyclovir can eliminate persistent Epstein-Barr virus (EBV) infection and thereby prevent EBV-associated lymphoma development in HIV-seropositive homosexual men.MethodPersistent EBV infection was examined in a group of 21 HIV-seropositive homosexual men before, during and after treatment with oral acyclovir at a dose of 800 mg every 6h (10 individuals) or with a placebo (11 individuals).ResultsIn 13 individuals, EBV was isolated from the oropharynx before and after treatment (seven cases from the acyclovir-treated group and six from the placebo-treated group). A significant reduction in virus isolation occurred during treatment in the acyclovir-treated group, but not in the placebo-treated group. In seven cases in whom EBV shedding was detected before and after treatment, the EBV strain isolated was identical throughout the study, even when acyclovir had abolished detectable shedding for the duration of the treatment. In two other cases more than one strain was detected. On examination of the EBV type present, 89% of a group of 18 patients consistently shed type A virus, 5.5% type B virus and 5.5% showed evidence of co-infection with both virus types. This compares with figures of 100, 0 and 0%, respectively, in a control group of HIV-seronegative individuals.ConclusionsHigh-dose acyclovir therapy does not eliminate persistent EBV infection from the oropharynx of healthy HIV-seropositive individuals and therefore would not necessarily prevent lymphoma development. Our results suggest that infection by type B EBV, and co-infections of both A and B type, are more common in HIV-seropositives than HIV-seronegatives.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1 -infected patients.MethodsProspective longitudinal follow-up of 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration ≥5mm). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl—Neelsen stains or grown in Lowenstein—Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations.ResultsActive TB developed in 23 out of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 $pM 11 months (range, 2–52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test but a positive Multitest developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and nine who converted during follow-up). Active TB developed in seven out of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in four out of 61 patients 3–27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years) and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 $pM 103 $$ 106/I (range/ −1–400 $$ 106/l).ConclusionsAmong HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 $$ 106/l, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo determine the frequency of pulmonary tuberculosis (TB) in patients with suspected Pneumocystis carinii pneumonia (PCP).DesignProspective study of sputum specimens from subjects undergoing diagnostic sputum induction for PCP and medical chart review.SettingUniversity hospital in the Bronx, New York City.PatientsA total of 373 consecutive adults with induced sputum specimens adequate for acid-fast smear and mycobacterial culture.Main outcome measures: Direct immunofluorescence for PCP, acid-fast stain, and mycobacterial culture of all induced sputum specimens. Determination of demographic characteristics, HIV risk factors, and HIV serological status. Clinical and radiographic findings of patients with TB.ResultsProven symptomatic HIV infection was present in 251 of the 373 (67%) patients prior to sputum induction. PCP was detected in 136 out of 519 (26%) specimens, Mycobacterium tuberculosis in 10 (1.9%) specimens from nine patients. Smear was positive for acid-fast bacilli in nine (1.7%), of which seven (78%) grew M. tuberculosis and two (22%) M. avium complex. Pulmonary TB was found in nine of the 373 (2.4%) patients [95% confidence intervals (CD, 1.1–4.6]. Smears were positive for acid-fast bacilli in seven out of 10 (70%) specimens with M. tuberculosis compared with two out of 65 (3%) with other mycobacteria (P < 0.0001). Of 66 specimens that grew mycobacteria despite negative acid-fast smears, three (4.5%) were M. tuberculosis (95% Cl, 0—13.3). Of the nine patients with TB, six had prior known TB, chest radiographs atypical for PCP, or both; two others had positive acid-fast smears. Only a single patient (0.27%; 95% Cl, 0—0.79) had pulmonary TB, which remained unsuspected after acid-fast smear of induced sputum.ConclusionsPulmonary TB occasionally occurs in patients with suspected PCP and in most cases is suggested by medical history, clinical findings, or acid-fast stain of induced sputum.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveMycobacterium genavense is a newly described pathogen that causes disseminated infection in AIDS. It is difficult to detect and identify due to its slow growth and fastidious nature. There is little information available about therapy for this new pathogen. We describe clinical and laboratory features and response to therapy in four patients with advanced AIDS complicated by disseminated M. genavense infection from Denver, Colorado, USA.Design and methodsRetrospective analysis of four cases identified in an AIDS clinic affiliated with a municipal hospital in Denver, Colorado. Clinical samples were inoculated onto BACTEC 12B, Lowenstein-Jensen, and Middlebrook 7H11 media.ResultsThe clinical features mimicked those of disseminated M. avium complex infection, with invasion of liver, spleen and lymph nodes with acid-fast bacilli (AFB). Acid-fast smears of blood and lymph nodes were positive; there was a modest increase in the growth index in BACTEC broth and tiny colonies appeared on Middlebrook agar. Patients were treated with combinations of antimycobacterial agents. Blood smears and cultures reverted to negative in treated patients. The best clinical response was associated with clarithromycin therapy.ConclusionsDisseminated disease due to M. genavense should be suspected among patients with the clinical presentation of disseminated M. avium complex infection and low growth index on BACTEC cultures for AFB. The diagnosis of M. genavense may be facilitated by performing acid-fast stains of samples from BACTEC bottles in such individuals. Clarithromycin therapy is associated with clinical improvement and clearance of bacteremia.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo study markers of progression in a cohort of HIV-infected intravenous drug users (IDU).DesignA prospective epidemiologic study.Setting and patientsWe studied progression of HIV infection among 126 IDU attending the Municipal Health Service in Amsterdam.Main outcome measuresProgression was defined as a decline of the CD4 cell countto <200 $$ 106/I on two consecutive follow-up visits or AIDS.ResultsUsing Cox modelling, the following baseline variables were predictive of progression. Enhanced progression was associated with: age > 30 years [relative hazard (RH), 7.7 [95% confidence intervals (CD, 1.7–36.0]], core antibody negativity [RH, 5.3 (95% Cl, 1.6–17.6)], CD4 cell count [for CD4 cells 350–500 $$ 106/I, RH, 1.38 (95% Cl, 0.37–5.16); for CD4 cells 200–350 $$ 106/l, RH, 9.20 (95% Cl, 2.73–31.05) compared with a CD4 count > 500 $$ 106/l]. A lower rate of progression was associated with borrowing used injecting equipment. IDU who reported borrowing injecting equipment between 1980 and baseline 10–99 times or >99 times had a RH of 0.44 (95% Cl, 0.22–0.88) and 0.19 (95% Cl, 0.03–0.37), respectively, compared with IDU who had borrowed <10 times. p24 antigen positivity was more predictive than core antibody negativity in a model with time-dependent variables, the relative risk for p24 antigen-positive participants was 3.5 (95% Cl, 1.3–9.3). Additional analysis of progression to AIDS in a larger group of IDU showed comparable results with regard to the effect of borrowing on progression.ConclusionsOur observation that those IDU who reported borrowing injecting equipment most frequently appeared to have the lowest rate of progression, corrected for some sources of potential confounding, requires further epidemiologic confirmation and extended laboratory studies since other sources of bias might have been present. Baseline CD4 count, age and core antibody or p24 antigen were predictive of progression in IDU. We wish to emphasize that our results do not imply that borrowing should be encouraged, but may have implications for our understanding of HIV pathogenesis.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID