ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To investigate whether the specificity of antibody responses to the gp120 V3 domain in HIV-1-infected individuals is related to the variability of this region.Methods:Sera from a cohort of 22 HIV-1-infected Ugandans were tested against peptides derived from each individual's autologous proviral V3 apex sequence. Autologous peptide reactivity was compared with reactivity to peptides derived from two Ugandan consensus sequences and previously isolated US/European and African viruses. Peptides from individuals with heterogeneous V3 apex sequences, representing different HIV-1 variants, were obtained and tested against the corresponding sera.Results:A notable cross-reactivity to different V3 apex peptides was observed. However, in the majority of sera, antibody reactivity to the autologous peptides was found to exceed reactivity to any of the other peptides tested. V3 proviral sequences from the Ugandan cohort studied have been shown to be closely related to the HIV-1MNisolate and thus, their sera gave better reactivity to V3MNand related peptides than to peptides representing other African HIV-1 isolates. In individuals with heterogenous V3 proviral sequences, we could distinguish divergent antibody responses to the genomic variants differing by single amino acids.Conclusion:Analysis of seroreactivity to peptides might constitute a relevant tool for investigating the variability of the HIV-1 gp120 V3 domain within infected populations and single individuals.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To investigate the possible role ofCryptococcus neoformansin HIV-1 pathogenesis.Design:Anin vitrosystem was developed to study HIV-1 replication in freshly HIV-1-infected peripheral blood mononuclear cells (PBMC) incubated with whole azide-killedC. neoformans.Methods:Human PBMC or peripheral blood lymphocytes were infected with lymphocytotropic HIV-1 and incubated with azide-killed encapsulated or non-encapsulatedC. neoformansfor 10 days. Viral replication was followed by HIV-1 p24 enzyme-linked immunosorbent assay and median tissue culture infective dose determination. Tumour necrosis factor (TNF) release by PBMC, induced byC. neoformans, was measured. Anti-TNF monoclonal antibodies or pentoxifylline were used to inhibit TNF bioactivity.Results:Both encapsulated and non-encapsulatedC. neoformansenhanced HIV-1 replication in PBMC but not in peripheral blood lymphocytes.C. neoformansinduced TNF release by PBMC. Inhibition of TNF bioactivity did not blockC. neoformans-enhancedHIV-1 replication in PBMC.Conclusions:C. neoformanscan enhance HIV-1 replication in T cells only in the presence of monocytic cells. This enhancement is not dependent on encapsulation nor can it be attributed to TNF release.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objectives and design:The expression of the accessory molecule CD28 was compared in various populations of T and natural killer (NK) cells from HIV-1-negative and HIV-1-positive individuals and correlated with activation using mitogensin vitro.Methods:Multiparameter flow cytometric analysis using combinations of CD3 CD28 and other markers was performed together with absolute cell counting in peripheral blood. Blast transformation and proliferative responses were also quantitated using the Cytoronabsoluteafter stimulation with phytohaemagglutinin (PHA) and anti-CD3. CD28− cells were also purified to confirm the observations.Results:In HIV-1-negative individuals >90% of CD3+ T cells were CD28+ and responded to stimulation, while CD3− CD16+ CD57+ NK-like cells were CD28-and failed to respond. In HIV-1-positive individuals the expression of CD28 was greatly reduced and the proportion of CD3+CD28− T cells expanded. CD8 lymphocytosis was caused entirely by the accumulation of CD28− T cells and many of these expressed activation markers human lymphocyte antigen-DR, CD38 and CD45RO on their membrane and molecules such as TIA-1 and perform, associated with cytolytic function, in their cytoplasm. The strong positive correlation (r = 0.66) between the lack of CD28 expression and the poor proliferation from HIV-1-positive individuals was confirmed by demonstrating that only CD28+ cells transformed into lymphoblasts and proliferated. Although the CD28− including CD3+ T cells transiently expressed CD25 (interleukin-2Rct), they did not undergo blastogenesis or activation measured by bromodeoxyuridine uptake and died after 3–4 days in culture. These observations were confirmed in costimulation experiments with anti-CD2 and anti-CD28.Conclusion:In HIV-1 infection activated CD3+CD28− T cells accumulate but are unresponsive to mitogens and anti-CD28. These cells appear to represent terminally differentiated effector cells which fail to respond to further stimuli because of the absence of a CD28 second signal.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:An HIV-associated superantigen (SAg) has been hypothesized. Here we test whether an SAg is functionally detectable in peripheral blood mononuclear cells (PBMC) from monozygotic twins discordant for HIV infection.Design and methods:The vβ selective T-cell depletion found in minor lymphocyte stimulation (Mls)-positive mice is caused by an SAg encoded by the mouse mammary tumour virus. Mis is a locus whose gene product stimulates a mixed lymphocyte reaction (MLR) in mice strains identical at the major histocompatibility complex locus. If an SAg is present in PBMC and/or sorted CD4+ cells from one HIV-infected monozygotic twin, it would stimulate PBMC from the corresponding healthy monozygotic twin in an MLR. In addition, if an SAg causes vβ-selective T-cell depletion in AIDS patients, a differential proliferation to a panel of staphylococcal enterotoxins (SE) of T lymphocytes from healthy and HIV-infected monozygotic twins should become measurable.Results:No positive MLR or significant differences in the SE-driven proliferation between the healthy and the HIV-infected twins were observed.Conclusions:Our results suggest that PBMC from the two HIV-infected twins do not express a functionally detectable SAg.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To document response to foscarnet salvage therapy in patients with cytomegalovirus (CMV) retinitis who are intolerant of or resistant to ganciclovir.Methods:Patients with AIDS and CMV retinitis who had documented hematologic intolerance or resistance to ganciclovir therapy received an induction course of foscarnet, 60mg/kg every 8h for 14 days, and subsequent chronic maintenance foscarnet therapy at a daily dose of 60, 90 or 120 mg/kg/day. The first 87 patients were randomly assigned to receive maintenance foscarnet at a dose of 60 or 90mg/kg/day; all subsequent patients were assigned a maintenance dose of 120 mg/kg/day.Results:A total of 156 evaluable patients were enrolled. Median time to retinitis progression and survival did not differ significantly among groups assigned to different maintenance foscarnet doses. Among patients with retinitis progression documented ophthalmologically occuring at ≤2 week intervals, despite optimal doses of ganciclovir, time to progression on foscarnet therapy was a median 8 weeks at all doses studied. By dose assignment, there were no significant differences in serious drug-associated toxicity, although trends toward increased renal and hypocalcemic adverse events were observed at higher maintenance doses.Conclusion:In patients intolerant of ganciclovir, salvage foscarnet therapy resulted in a longer time to retinitis progression than reported previously in historic controls who terminated ganciclovir therapy. In patients who exhibited clinical resistance to ganciclovir, foscarnet appeared to have efficacy in controlling retinitis. No significant differences in either efficacy or toxicity were observed in the range of foscarnet maintenance doses studied.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To determine criteria for the diagnosis of cytomegalovirus (CMV) colitis and to analyse stages of the course and prognosis of CMV colonic involvement in HIV-1-infected patients.Design:Prospective search for CMV colonic involvement with systematic biopsies to search for CMV intranuclear inclusion bodies and for CMV culture. The evolution of CMV colonic involvement was estimated using further coloscopies and autopsy.Setting:Infectious diseases department in a tertiary referral teaching hospital in Paris, France.Participants:Fifty-five consecutive patients with HIV-1 infection, who had not previously received anti-CMV drugs, and who had at least one coloscopy performed.Results:According to initial coloscopy, colitis, either ulcerative or inflammatory, was found in nine (16%) out of the 55 patients, CMV intranuclear inclusions were present in the colon of four (7%) patients, and colonic cultures were positive for CMV in 15 (27%) patients. The results of the initial coloscopy showed a positive correlation between endoscopic colitis (either ulcerative or inflammatory), CMV inclusions and positive CMV culture from colonic biopsies. The absence of endoscopic ulcerative lesions had a 98% (49 out of 50) negative predictive value for recording CMV inclusions in the colon (95% confidence interval, 89–100). CMV inclusions were recorded in three out of five ulcerative colitis. Male homosexuality, HIV-1 infection stages IVB, C1, D or E, according to the Centers for Disease Control and Prevention classification, CD4 lymphocyte count <200×106/l and CMV viraemia also correlated positively with CMV colonic involvement. During the observation period (mean, 7.3 months), the estimated incidence of CMV colitis according to coloscopic studies was 13%. Deterioration in condition was the most frequent spontaneous evolution of CMV colonic infection, whereas anti-CMV treatment resulted in an improvement. Ulcerative lesions occurred earlier in patients with colonic CMV inclusions or positive colonic CMV culture than in patients without CMV colonic involvement at the initial coloscopy. CMV colitis occurred late in the course of HIV-1 infection, on average 4 months before death. The presence of CMV inclusions was an indicator of poor prognosis with earlier occurrence of CMV viraemia and retinitis and no survival after 9 months.Conclusions:These results confirm that the colon is a target organ for CMV in HIV-1-infected patients. Coloscopy should be used to diagnose CMV colitis, because of the close correlation between endoscopic and histological data (i.e., intranuclear inclusions). This combination allows us to propose an evolutive staging of CMV colonic involvement and provide stratification criteria to assess the efficacy of anti-CMV drugs.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To establish when the formation of antibodies against T-lymphocyte-dependent and -independent antigens is impaired during HIV infection.Design:Prospective study on antibody formation before and 30 days and 60 days after vaccination with tetravalent influenza vaccine, tetanus toxoid and pneumococcal vaccine; booster with influenza vaccine was administered 30 days after initial vaccination.Setting:Outpatient clinic of University Hospital Leiden.Participants:Fifty-one HIV-infected individuals and 10 healthy controls.Results:In HIV-infected individuals with <100×106/l CD4+ lymphocytes almost no influenza antibodies were formed; CD4+ counts between 100 and 300 x 106/l correlated with suboptimal antibody formation; CD4+ counts ≤300x106/l yielded more individuals with protective antibody titres. Thirty days after vaccination, protective antibody titres against the four influenza strains had been achieved in 24% of all HIV-infected individuals for A/Beijing (H3N2) (controls, 90%), 59% for A/Taiwan (H1N1) (controls, 80%), 18% for B/Beijing (controls, 30%) and 37% for B/Panama (controls 90%). Booster vaccination after 1 month did not increase antibody levels. Anti-tetanus toxin antibody formation, which is also T-lymphocyte-dependent, was correlated with the number of CD4+ lymphocytes. After pneumococcal vaccination (T-lymphocyte-independent), normal antibody formation was observed in HIV-infected individuals, including those with low CD4+ counts.Conclusions:Influenza vaccination should not be administered to HIV-infected individuals with CD4+ counts <100×106/l; pneumococcal vaccination can be offered to all HIV-infected individuals and a tetanus toxoid booster should be administered when indicated.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To assess the joint use of purified protein derivative (PPD) and delayed-type hypersensitivity (DTH) antigens in screening individuals of unknown HIV serostatus for tuberculosis (TB) preventive therapy eligibility.Design:Population-based survey.Methods:A group of migrant farm workers were screened for HIV and skin-tested with PPD, tetanus toxoid (TET),Candida albicans(CAN) and mumps (MUM) antigens by the Mantoux method. Anergy was defined as a ≤2mm reaction to all four antigens. Eligibility for preventive therapy was defined as a reaction of ≥5 mm to PPD among HIV-seropositive individuals, ≥10mm among HIV-seronegatives, or anergy.Results:A total of 253 out of 271 individuals had sufficient data for analysis. Of these, 15 (5%) were HIV-seropositive; 183 (75%), 175 (72%) and 157 (65%) reacted to TET, CAN, and MUM, respectively, and 113 (47%) were eligible for preventive therapy [108 (44%) PPD-positive, five (2%) anergic]. Use of PPD alone was 95% sensitive for detecting preventive therapy eligibility; PPD plus one DTH antigen was more sensitive (99%) but less specific (range, 69–85%); PPD plus two DTH antigens was most specific (CAN + MUM, 84%; TET + MUM, 93%; and TET + CAN, 100%).Conclusions:In this population with 5% HIV seroprevalence, testing for anergy did not significantly increase the detection of preventive therapy eligibility. The use of two DTH antigens is very sensitive and specific. These results support the recommendation of joint PPD and anergy testing for the screening of HIV-seropositive individuals. Our data also suggest, however, that for individuals whose HIV serostatus is unknown, anergy testing should be considered as a screening tool only if the prevalence of anergy is expected to exceed the prevalence of PPD positivity.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To studyToxoplasmaencephalitis (TE) in advanced HIV infection, including predictive factors, possible prophylactic regimens and impact on survival.Design:Epidemiological analysis of data collected prospectively during the Alpha study, a double-blind, randomized clinical trial, comparing two doses of dideoxyinosine in patients with advanced HIV disease.Patients:First episode of TE occurred in 75 out of 499 patients participating in the trial.Methods:Kaplan-Meier estimates and semi-parametric Cox's model were used.Results:A low CD4 cell count and a positiveToxoplasmaserology were strongly predictive of the occurrence of TE. In patients with CD4 counts < 100×106/l and a positiveToxoplasmaserology at entry to the study, the 12-month TE incidence was 25.4%. Patients who were receiving at entry any of the following potentially antitoxoplasmic drugs: trimethoprim-sulphamethoxazole, pyrimethamine, dapsone, pyrimethamine-sulphadoxine or sulphadiazine, had a lower TE incidence than those who were not; 6.2 versus 18.8%, respectively (P<0.001). The rate of survival 12 months after TE was 29.6%. Even after adjusting the major prognostic covariates, TE was predictive of death (P<0.001; relative risk, 1.8).Conclusions:The high HIV incidence, morbidity and mortality in high-prevalence areas suggests that primary prophylaxis should be given in patients at high risk for toxoplasmic reactivation.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID