摘要:

Objective:Sexual transmission of HIV is the most common route of HIV transmission throughout the world. To prevent sexually transmitted HIV infection, a vaccine is urgently needed. A previous report demonstrated the targeted immunization of the iliac lymph nodes with simian immunodeficiency virus (SIV) subunits protects rhesus macaques from rectal challenge with SIV. We sought to determine whether this immunization strategy could protect rhesus macaques from vaginal challenge with SIV.Design:Macaques were immunized with either whole-killed SIV or envelope and core subunit antigen vaccines. Using three independent groups, with three macaques in each group, macaques were immunized by the targeted iliac lymph-node (TILN) route, injecting the vaccine close to the iliac lymph nodes that drain the genital tract.Results:The TILN immunization procedure induced high-titer SIV-specific immunoglobulin (Ig) G antibodies in serum in all animals and anti-SIV IgG and IgA antibodies in the cervicovaginal secretions of most animals. After a series of three or four TILN immunizations, the animals were intravaginally challenged with SIVmac251. All animals became virus isolation-positive, except one animal immunized with SIV p27 and gp120. This animal was virus isolation-negative but SIV DNA proviral sequences were detected in peripheral blood mononuclear cells.Conclusions:In this series of studies, reliable protection from vaginal transmission of SIV was not achieved by the TILN immunization procedure.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To evaluate the immunogenicity and prophylactic efficacy of immunization schemes employing a recombinant canarypoxvirus (‘ALVAC’)-based feline immunodeficiency virus (FIV) vaccine alone or in combination with an inactivated FIV-infected cell vaccine against homologous and heterologous FIV challenges in cats.Methods:Specific pathogen-free cats were given a total of three immunizations with subtype A vaccines and challenged 4 weeks after the final immunization with 50 median animal infectious doses (ID50) of FIV-Petaluma, a subtype A isolate. Following the initial challenge, protected cats received a second challenge with 75 ID50of FIV-Bangston, a subtype B isolate. FIV-specific humoral and cell-mediated responses were measured to determine the immune correlates of protection.Results:Two of three cats immunized with the ALVAC-FIV recombinants alone were protected from homologous FIV challenge in the presence of FIV-specific cytotoxic T-lymphocyte (CTL) responses but in the absence of FIV-specific humoral responses. All three cats immunized with the ALVAC-FIV recombinant and boosted with FIV-infected cell vaccine were also protected from homologous FIV challenge in the presence of both FIV-specific CTL and humoral responses. Partial to full protection was observed in ALVAC-FIV/FIV-infected cell vaccine-immunized cats against a heterologous FIV challenge given 8 months after the initial challenge. Two out of three cats had transient infection and the remaining cat had no sign of FIV infection at a dose at which all three control cats were readily infected.Conclusions:Immunization schemes employing ALVAC-based FIV vaccines in combination with inactivated FIV-infected cell vaccine generate protective immune responses that can cross-react with FIV isolates that are genetically distinct from the vaccine strains.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background:The growth of Kaposi's sarcoma (KS) spindle cells is dependent on a number of inflammatory cytokines as well as the autocrine growth factor, basic fibroblast growth factor (bFGF). Moreover, inflammatory cytokines, found at increased levels in KS lesions, promote bFGF production in KS and endothelial cells.Objectives:To determine the induction of bFGF isoforms, role of bFGF in cell growth and activation of the bFGF promoter by inflammatory cytokines.Design and method:3H-Thymidine uptake, bFGF immunoblotting and transfection of dominant-negative MAP kinase components were used to study the effect of cytokines on the bFGF promoter, bFGF isoform expression and proliferation of KS cells.Results:Treatment with oncostatin M (OSM), interleukin (IL)-1 and tumor necrosis factor (TNF)-α induced the expression of 18, 22 and 24 kDa bFGF isoforms in KS and human umbilical vein endothelial cells (HUVEC). Antisense bFGF oligonucleotides interfered in the induction of KS cell proliferation by individual cytokines. OSM, IL-1 and TNF-α induced the transcriptional activation of a bFGF promoter reporter gene in parallel with the activation of an AP-1 reporter. Dominant-negative ERK and dominant-negative JNK mutants interfered in cytokine-induced activation of these reporters in accordance with the role of the MAP kinase cascades in individual cytokine signaling pathways.Conclusions:OSM, IL-1 and TNF-α induce KS cell growth by inducing the expression of various bFGF isoforms. Moreover, bFGF production by KS and HUVEC is dependent on the activation of the ERK and JNK cascades, which result in the transcriptional activation of the bFGF promoter.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To assess the impact of opportunistic diseases on survival in patients with HIV disease.Methods:A cohort of 2081 patients followed for a mean of 30 months was studied. Time-dependent Cox proportional hazards analyses were performed using incident opportunistic diseases and CD4 cell counts as independent variables.Results:During follow-up, 730 (35%) patients died. The occurrence ofPneumocystis cariniipneumonia (PCP), cytomegalovirus (CMV) disease,Mycobacterium aviumcomplex (MAC) disease,Candidaesophagitis, Kaposi's sarcoma, lymphoma, progressive multifocal leukoencephalopathy (PML), dementia, wasting, toxoplasmosis, and cryptosporidiosis were all significantly associated with death, independently of CD4 cell count (allP< 0.001 for opportunistic diseases controlling for CD4 cell count). The magnitude of increased risk was greatest for lymphoma [relative hazard (RH), 7.2], PML (RH, 3.9), MAC (RH, 3.0) and CMV (RH, 2.2). Cryptococcosis (RH, 0.94) and herpes zoster (RH, 0.85) were not associated with death. In a multivariate Cox proportional hazards analysis, MAC [RH, 2.56; 95% confidence interval (CI), 2.1–3.1], CMV (RH, 1.63; 95% CI, 1.3–2.1), toxoplasmosis (RH, 1.85; 95% CI, 1.3–2.6), PCP (RH, 1.29; 95% CI, 1.1–1.5), and CD4 cell count were significantly associated with death. Patients who had opportunistic diseases had significantly greatly monthly declines in CD4 counts (−11 × 106/l per month) than those who did not (−6 × 106/l per month;P< 0.001).Conclusion:Most opportunistic diseases increase the risk of death independently of CD4 cell count. These data support the hypothesis that opportunistic diseases enhance HIV pathogenesis and further underscore the importance of prophylaxis.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background:A substantial number of patients with advanced HIV infection suffer from intractable diarrhoea. The aim of this study was to evaluate whether potent antiretroviral therapy could alleviate such diarrhoea.Methods:In an open randomized study the effect of the HIV protease inhibitor indinavir in combination with nucleoside analogue reverse transcriptase inhibitors on chronic HIV-related diarrhoea was investigated in 14 late-stage (CD4+ lymphocyte count ≤ 50 × 106cells/l) HIV-infected patients. Data concerning stool frequency, stool consistency and antidiarrhoeal drug use were collected in daily diaries over a 24-week period. Endpoints of the study were reduction of stool frequency, improvement of stool consistency, weight gain, and in case of diarrhoea due to Enterocytozoon bieneusi or Cryptosporidium sp. disappearance of these parasites from stool.Results:Thirteen patients started the study drug indinavir. One patient died after 1 week and one patient withdrew prematurely after 18 weeks. Median stool frequency declined from 5.8 daily at baseline to 2.3 daily after 24 weeks (P= 0.04). Stool consistency improved considerably over the study period: before treatment 56% of stools were watery and 0% were formed; at week 24 these figures were 0 and 35%, respectively. Body weight increased significantly with a median increment of 6.6 kg at week 24 (P= 0.0006). In two out of six patients with microsporidiosis and both patients with cryptosporidiosis, stools were free of parasites at week 24. Five out of six patients who used non-specific antidiarrhoeal medication on a regular basis prior to the study had ceased to do so at the end.Conclusion:The use of potent antiretroviral therapy in patients with advanced HIV infection can improve chronic HIV-related diarrhoea and in some cases lead to disappearance ofE. bieneusiandCryptosporidium sp.from the stools.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objectives:To characterize diarrhoeal mechanisms in HIV-infected patients, epithelial transport and barrier function of the duodenal mucosa was investigatedin vitro.Patients:Twenty-one HIV-seropositive patients (13 asymptomatic and eight with diarrhoea) and 12 controls from an urban referral-based tertiary care centre in Berlin who underwent duodenoscopy.Methods:A new miniaturized Ussing chamber allowed measurements on duodenal forceps biopsies. Epithelial barrier function was characterized by alternating current impedance analysis, which allows differentiation of epithelial and subepithelial resistance and by3H-lactulose and3H-mannitol flux measurements. Na+-glucose cotransport was quantified as phlorizin-sensitive short circuit current (ISC) and active ion secretion by baseline and bumetanide-sensitive ISC.Results:Duodenal biopsies from asymptomatic HIV-infected patients were no different from controls, whereas biopsies from HIV-infected patients with diarrhoea showed a decrease in epithelial resistance from 21.2 ± 1.9 to 12.9 ± 1.3 Ωcm2(P< 0.01). Concomitantly, mucosal-to-serosal lactulose flux increased from 0.29 ± 0.02 to 0.40 ± 0.03 µmol (hcm2) (P< 0.01). Phlorizin-sensitive ISCindicating Na+-glucose cotransport, as well as baseline and bumetanide-sensitive ISCindicating active electrogenic chloride secretion were not different between the three groups.Conclusions:A miniaturized Ussing device was developed for electrophysiological investigations of duodenal forceps biopsies, which allowed characterization of active ion transport mechanisms and epithelial barrier function. Duodenum of HIV-infected patients with diarrhoea showed no evidence for active ion secretion or Na+-glucose malabsorption, but showed an impaired epithelial barrier function, which could contribute to diarrhoea by a leak flux mechanism.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To evaluate the effects of an oral nutritional supplement enriched with two potentially immunostimulant compounds (arginine and Ω-3 fatty acids) on the changes in food intake, body composition, immune parameters and viraemia in HIV-infected outpatients.Design:Six-month prospective randomized double-blind controlled study.Setting:University hospital outpatient nutrition clinic.Patients:Sixty-four HIV-infected outpatients with CD4 lymphocyte count ≥ 100 × 106/l.Intervention:All patients received a daily oral nutritional supplement (606 kcal supplemented with vitamins, trace elements and minerals). In addition, half of the patients were randomized to receive 7.4 g arginine plus 1.7 g Ω-3 fatty acids.Main outcome measures:Disease progression measured by AIDS-defining events, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors, nutritional status determined by anthropometric, bioelectrical impedance and dietetic assessment.Results:Fifty-five patients completed the protocol. Compliance with and tolerance of oral nutritional supplement during the 6-month period was excellent. In both groups of patients the following were found: total energy intake was transiently increased and then returned to baseline level; nitrogen/energy intake ratio was increased throughout the study; gain of body weight and fat mass were approximately 2 and 1 kg, respectively, over 6 months, and were similar in both groups. In addition, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors remained statistically unchanged and were similar in both groups.Conclusions:Enrichment of an oral nutritive supplement with arginine and Ω-3 fatty acids did not improve immunological parameters. However, body weight increased in both groups.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To assess the effect of filgrastim treatment on the incidence of severe neutropenia in patients with advanced HIV infection, and the effect of initial filgrastim treatment on prevention of infectious morbidity.Design:Randomized, controlled, open-label, multicenter study.Setting:Outpatient centers and physician offices.Patients:Men and women aged > 13 years, who were HIV antibody-positive, and had a CD4 cell count < 200 × 106/l, absolute neutrophil count (ANC) 0.7−1.0 × 109/l, and platelet count ≥ 50 × 109/l within 7 days of randomization were eligible. Two hundred and fifty-eight patients entered and 201 completed the study.Intervention:Daily filgrastim (starting at 1 µg/kg daily, adjusted up to 10 µg/kg daily) or intermittent filgrastim (starting at 300 µg daily one to three times per week to a maximum of 600 µg daily 7 days weekly) was administered to maintain an ANC between 2 and 10 × 109/l. Patients in the control group received filgrastim if severe neutropenia developed.Main outcome measures:Incidence of severe neutropenia (ANC < 0.5 × 109/l) or death, incidence of bacterial and fungal infections, duration of hospitalization and intravenous antibacterial use, and safety.Results:The primary endpoint of severe neutropenia or death was less frequent in patients who received daily (12.8%) or intermittent (8.2%) filgrastim compared with control patients (34.1%;P< 0.002 andP< 0.0001 for comparison with daily and intermittent groups, respectively). Filgrastim-treated patients developed 31% fewer bacterial infections and 54% fewer severe bacterial infections than control patients, required 26% less hospital days including 45% fewer hospital days for bacterial infections, and needed 28% fewer days of intravenous antibacterials. Filgrastim was not associated with an increase in HIV-1 plasma RNA level in a subset of patients in whom this was measured or any new or unexpected adverse events.Conclusion:Filgrastim was safe and effective in preventing severe neutropenia in patients with advanced HIV infection, and may reduce the incidence and duration of bacterial infections, incidence of severe bacterial infections, duration of hospital days for infections, and days of intravenous antibacterial agents.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objectives:To determine the risk factors for HIV seroconversion and assess the association between contraceptive use and HIV infection among women attending three large family planning clinics in Dar es Salaam, Tanzania.Design:Prospective cohort study.Methods:Between 1992 and 1995, 2471 HIV-negative women were followed prospectively. Information about sociodemographic characteristics, sexual behavior, contraceptive use and other risk factors was collected at recruitment and updated at follow-up visits. At the end of the study, specimens were collected for HIV testing and laboratory diagnosis of sexually transmitted diseases.Results:The overall HIV incidence was 3.4 per 100 person-years [95% confidence interval (CI), 2.6–4.1]. The risk of HIV seroconversion decreased with increasing age (P= 0.04, test for trend). Women reporting three or more sex partners during the follow-up period had the highest risk of HIV [age-adjusted relative risk (RR), 4.89; 95% CI, 2.6–9.17]. Having an uncircumcised husband was associated with a significantly increased risk of HIV (age-adjusted RR, 3.60; 95% CI, 1.1–11.59). The risk of HIV was also significantly increased among women with gonorrhoea (age-adjusted RR, 3.51; 95% CI, 1.6–7.71) and candidiasis at baseline (age-adjusted RR, 1.98; 95% CI, 1.1–3.33) and among women reporting alcohol consumption during the follow-up period. After controlling for other risk factors, the risk of HIV infection amongst users of oral contraceptive, intrauterine device and injectable contraceptive was not significantly increased. Similarly, there was no significant trend associated with increasing duration of use of any of these contraceptive methods.Conclusion:These findings confirm that a large number of new HIV infections continue to occur in this population. Reassuringly, no significant association was observed between HIV and use of specific contraceptive methods. Interventions to reduce further spread of HIV are still urgently needed.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objectives:To study trends in AIDS incidence in Europe by age and year of birth.Design:Age-period-cohort analyses were adopted to distinguish the different time factors of calendar year, age and year of birth.Methods:Non-aggregate AIDS incidence data from 12 European countries (1978–1994) were adjusted for reporting delay and expressed per unit of population (per 100 000 persons or 100 000 person-years). Age-specific incidence patterns (absolute level and rate of increase) were compared between 5-year birth cohorts for homo-/bisexual men, injecting drug users (IDU) and heterosexual contact cases.Results:Mean age at diagnosis increased strongly amongst IDU, but less so among homo-/bisexual men and heterosexual contact cases. Of a total 110 646 reported cases (116 311 after adjustment for reporting delay), 87 167 (78.8%) were among people born in 1950–1974 [91 951 (79.1%) after adjustment for reporting delay]. The relative impact on specific birth cohorts differed strongly by exposure group. Incidences at age ranges of 20–24 and 25–29 years among cohorts born in 1965 and after were about the same level (homo-/bisexual men, IDU) or higher (heterosexual contact cases) than older birth cohorts when these were in the same age range; rates of increase were less among homo-/bisexual men and IDU, but higher among heterosexuals. There were large differences between counties.Conclusions:Overall, AIDS incidence among cohorts born in 1965 and after is about the same level (homo-/bisexual men, IDU) or higher (heterosexual contact cases) than older cohorts when these were in the same age range. Rates of increase of AIDS incidence curves suggest reduced HIV transmission amongst the most recent cohorts of homo-/bisexual men and IDU, but among young heterosexuals the epidemic is still expanding.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID