ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo identify antigenic regions in the envelope glycoproteins of the simian immunodeficiency virus isolate, SIVsm.MethodsThirty-eight peptides were synthesized and used in site-directed enzyme-linked immunosorbent assays with sera from experimentally infected macaques.ResultsFour antibody-binding regions were identified, corresponding to the second variable region [V2; amino acids (aa) 170–196], the region homologous to V3 in HIV-1 (aa 313–346), the carboxy terminus of gp120 (aa 514–537) and the amino terminus of the transmembrane protein (aa 608–638). Serum reactivity to the V2 region was higher in surviving monkeys than in animals with an early development of simian AIDS. The antigenicity of the peptide appears to be conformationally dependent.ConclusionsThe majority of antigenic sites identified in the envelope proteins of SIV correspond to sites identified in HIV-1 and HIV-2, which further supports the use of the simian model in vaccine development. The pattern of reactivity to the V2 region suggests that absence of antibodies directed to this site might correlate with disease progression.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveFine mapping of HIV-1 gp41 fusion-critical sites.Design and methodsAntibodies from human HIV-1-positive sera were affinity-purified on a panel of synthetic overlapping peptides spanning residues 526–682 of the extracellular portion of HIV-1 gp41. The syncytium-inhibiting capacity of the immunopurified antibodies and their differential reactivity on the synthetic peptides were tested.ResultsThis approach enabled the identification of residues 583–591 (ARILAVERY), 595–599 (QQLLG), 603–609 (CSGKLIC) and 664–673 (ELLELDKWAS) as possibly involved in the fusion process. Reduction in the anti-ARILAVERY, anti-CSGKLIC and anti-ELLELDKWAS antibody titres and frequencies correlates with disease progression. Syncytia-inhibition capacity of sera did not correlate with the presence of high-titre antibodies reacting with any of the peptides tested, suggesting that most fusion-affecting antibodies are not directed towards gp41.ConclusionsThis strategy may be relevant for understanding the contribution of anti-gp41 antibodies in protecting against the pathogenic effects of the virus and in the design of an effective env vaccine.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo assess the risk of developing weight loss, a decline in CD4 + T-cell count and AIDS-defining infections using urinary neopterin levels and CD4+ T-cell count.DesignRetrospective record review.SettingA primary care clinic for patients at any stage of HIV infection at the University Hospital in Innsbruck, Austria, to which all patients with HIV-related diseases from the Austrian Tyrol are referred.Patients, participantsSeventy-nine out of the 311 HIV-seropositive individuals attending our clinic between July 1985 and December 1991 participated in the study. The selection was made after complete examination (clinical and laboratory) and follow-up of at least 6 months, up to 48 months (median, 28 months). Patients with severe diarrhoea were excluded.Main outcome measuresCorrelation between body mass index, urinary neopterin and CD4 + T-cell count; development of AIDS-defining infections, weight loss, and a decline in CD4 + T-cells. Weight loss was recognized if > 10% of body weight, and there had been no concomitant AIDS-defining infection for at least 2 months.ResultsInitial urinary neopterin (P = 0.04), but not initial CD4 + T-cell count (P = 0.94), correlated with the body mass index obtained at the end of follow-up. Using the product-limit method, urinary neopterin predicted weight loss (P< 0.0001), decline in CD4+ T-cell count to < 200 x 106/1 (P = 0.006) and AIDS-defining infections (P = 0.009). CD4 + T-cell count was a better predictor of AIDS-defining infections (P < 0.0001) than of weight loss (P = 0.002). Results were confirmed by multivariate analysis.ConclusionsWeight loss > 10% of body weight is associated with immune activation.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo describe the characteristics of individuals ≥ 13 years of age with HIV wasting syndrome in the United States and US territories.Design: Retrospective review of national AIDS case surveillance data.MethodsData for the 147225 individuals with AIDS reported to the Centers for Disease Control from 1 September 1987 to 31 August 1991 were reviewed. The frequency of HIV wasting syndrome and its association with demographic and exposure category variables and with other AIDS-indicator diseases were assessed.ResultsA total of 10525 (7.1%) had wasting syndrome as the only AIDS-indicator condition, and 15726 (10.7%) had wasting syndrome plus at least one other AIDS-indicator condition. Patients with wasting syndrome as the only AIDS diagnosis were more likely to be female, to be black or Hispanic, and to have a mode of HIV exposure reported as injecting drug use, heterosexual contact, or transfusion/hemophilia. The proportion of AIDS patients reported with wasting syndrome varied by geographic distribution, ranging from 11% in the northeastern United States to 47% in Puerto Rico. The association between HIV wasting syndrome and Hispanic ethnicity was due to the much higher prevalence of wasting syndrome reported in Puerto Rican AIDS patients. The other AIDS-indicator conditions most strongly associated with wasting syndrome were isosporiasis, pulmonary candidiasis, esophageal candidiasis, HIV encephalopathy, chronic mucocutaneous herpes simplex, and coccidioidomycosis.ConclusionsThe association between HIV wasting syndrome and injecting drug use, and the significant racial/ethnic and geographic differences in prevalence of this AIDS diagnosis may reflect differences in diagnostic and reporting practices and/or access to medical care.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo describe the rate of development of in vitro HIV resistance to zidovudine (ZDV) and its prognostic implications within the Multicentre Canadian AZT Trial (MCAT).MethodsHIV-infected subjects in Centers for Disease Control (CDC) stages IIB, III and IVC-2 with CD4 cell counts > 270 x 106/I were treated with ZDV as part of a dose-range study. Participating volunteers underwent prospective clinical and laboratory evaluations at regular intervals. Viral cultures and sensitivity testing were performed every 12 weeks in a predefined subset of 50 volunteers. An isolate was designated ZDV-resistant if it had a median inhibitory concentration (IC50) for ZDV at least 50-fold higher than that of virus isolated from the same subject before initiation of antiviral chemotherapy. The relationship between resistance and subsequent disease progression was studied using the Mantel and Byar method, for which, at each instance of disease progression, 2 x 2 tables classifying progression versus resistance status were constructed. The observed number of progressions was compared with that expected under the null hypothesis using Mantel-Haenszel methods adjusted for baseline CD4: CD8 ratio.ResultsThe Kaplan-Meier estimate for the cumulative development of in vitro resistance was 64% [95% confidence interval (CI), 41–78] at 180 weeks. Baseline CD4: CD8 ratio was negatively associated (P = 0.10) with the subsequent development of resistance (proportional hazard, 0.44; 95% CI, 0.17–1.10). After adjusting for baseline CD4:CD8 ratio, the numbers of observed and expected progressions following the development of resistance were 15 and 7.6, respectively (P = 0.008). A similar relative risk of progression between resistant and non-resistant states was found in the two CD4:CD8 strata; observed and expected progressions were 4 and 2.3 and 11 and 5.2 in the high and low CD4: CD8 strata, respectively.ConclusionsIn vitro resistance to ZDV developed in 64% of subjects after 180 weeks of ZDV therapy. Lower CD4: CD8 ratio at baseline was associated with faster development of resistance. In addition, the development of resistance was found to be a marker of subsequent disease progression. This association persisted after adjustment for baseline CD4: CD8 ratio. Whether in vitro resistance to ZDV is merely a surrogate marker or a determinant of disease progression remains to be established.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo evaluate the efficacy and safety of zidovudine (ZDV) at a maintenance dose of 250 mg every 6 h alone or as cotherapy with acyclovir (ACV; 800 mg every 6 h) as treatment for AIDS and AIDS-related complex (ARC).DesignDouble-blind, randomized, placebo-controlled clinical trial of up to 1 year's therapy.SettingTeaching hospital ambulatory clinics in eight European countries and Australia.SubjectsA total of 131 patients with AIDS and 134 with ARC were enrolled and followed from 1986 to 1988.Main outcome measuresTime to development of AIDS-defining opportunistic infections and AIDS-associated neoplasms, survival assessed at 1 year after entry, performance status, body weight, CD4 + cell counts.ResultsDuring the study period, 46 (36%) ZDV recipients and 37 (27%) cotherapy recipients developed opportunistic infections. The probability of an ARC patient progressing to AIDS (1982 Centers for Disease Control criteria) was 0.18 and 0.15 [95% confidence interval (CI) for difference, —0.17 to 0.11] for the ZDV alone and cotherapy recipients, respectively. After excluding patients who experienced an opportunistic infection during the first 4 weeks of therapy, the probability was 0.13 and 0.099 (95% Cl for difference, —0.16 to 0.10) for the ZDV and cotherapy recipients, respectively. Thirty-six patients treated with single-agent therapy [28 (41%) AIDS and eight (12%) ARC patients] and 15 cotherapy recipients [13 (21%) AIDS and two (3%) ARC patients] died during the study. There was a significant difference in time to death between the cotherapy and ZDV alone groups for both AIDS (P = 0.014) and ARC (P = 0.045) patients, with cotherapy patients surviving longer. Infections related to herpesviruses, but not cytomegalovirus, were reduced in patients receiving ACV therapy. CD4 + cell counts in both arms generally increased initially and then declined. Forty-six per cent of patients in the ZDV group (59% of AIDS and 31% of ARC patients) and 52% of patients in the cotherapy group (69% of AIDS and 34% of ARC patients) experienced bone-marrow suppression. Red cell transfusions were administered to 33% of ZDV alone recipients and 34% of cotherapy recipients.ConclusionThese data show that the addition of high-dose ACV cotherapy to ZDV for patients with AIDS and advanced ARC results in a statistically significant improvement in survival with minimal increase in the risk of toxicity.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo compare the effect of two dose regimens of zidovudine in the treatment of severe HIV-related thrombocytopenia (TP).Design: Eighty-four patients with severe HIV-related TP and platelet counts < 50 x 109/I were enrolled in an open study at six centres. Patients were randomized into two groups to receive zidovudine (group A, 500 mg per day; group B, 1000 mg per day) for 6 months.MethodsPlatelet counts were determined monthly and patients categorized as complete responders (CR; platelets > 100 x 109/I), partial responders (PR; platelets > 50 to < 100 x 109/I), or failures (F; platelets to < 50 x 109/I). CD4+ and CD8 + lymphocytes, HIV antigenaemia, β2-microglobulin, white blood cells, mean cell volume and haemoglobin were also determined.ResultsSeventy-one patients (35 and 36 in groups A and B, respectively) completed the study; 11.4% of group A patients were CR and 45.7% PR; 38.9% of group B were CR and 33.3% PR. Increase in mean platelet counts was dose-related, more rapid in the higher dose group and remained significantly higher after 6 months of treatment (56.4 x 109/I in group A versus 98.2 x 109/I in group B; P < 0.01).ConclusionsThe results confirm the efficacy of zidovudine in the treatment of severe HIV-related TP. The average for CR and PR in the two groups was 64.8%; the higher dose of zidovudine was more effective at increasing platelet counts.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo determine whether specific intestinal parasites are associated with HIV infection in Tanzanian children with chronic diarrhea.DesignA prospective, cross-sectional study.SettingMuhimbili University College of Health Sciences, Dar es Salaam, Tanzania.SubjectsAll children aged 15 months to 5 years admitted with chronic diarrhea, and age-matched controls.MethodsStandardized history, physical examination, HIV serology, and stool parasitology were evaluated for all subjects. We compared three groups: HIV-infected and non-HIV-infected children with chronic diarrhea and controls without diarrhea.Main outcome measuresFecal parasites and nutritional status.ResultsChronic diarrhea accounted for one-quarter of all cases of diarrheal disease in the defined age range, and children with chronic diarrhea were severely malnourished. Forty per cent of subjects with chronic diarrhea were HIV-seropositive. Although intestinal parasites were detected in approximately 50% of all three groups, diarrheagenic parasites were detected in up to 40% of children with chronic diarrhea. Blastocystis hominis was detected only in HIV-infected patients.ConclusionsHIV infection was common in children with chronic diarrhea, and parasitic agents of diarrhea may be important in children with chronic diarrhea both with and without HIV infection in this setting. B. hominis was more frequent in HIV-infected children. The immunocompromising effects of severe malnutrition may have diminished the difference between HIV-infected and non-HIV-infected children.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

ObjectiveTo evaluate plasma levels of vasoactive intestinal peptide (VIP) in AIDS patients with refractory idiopathic diarrhoea, and to assess the role of treatment with octreotide.PatientsThree AIDS patients were evaluated for severe watery diarrhoea of 2–6 months' duration, which was complicated by weight loss, weakness, and fluid and electrolyte abnormalities. They had not shown a significant response to several regimens of empirical antimicrobial chemotherapy, or symptomatic antidiarrhoeal treatment.MethodsA complete diagnostic examination, including repeated microbiological evaluation and radiological, ultrasonographic, endoscopic and histological examination, was performed. Plasma levels of VIP were determined by radioimmunoassay and compared with concentrations in a group of healthy subjects.ResultsSince no clinically significant results were obtained from standard diagnostic evaluation and empirical therapeutical attempts, idiopathic refractory diarrhoea was diagnosed. Plasma concentrations of VIP were moderately elevated in all three subjects examined, with levels of 11.5, 17.5 and 9.5pmol/l (values < 8.8pmol/l in the control group). One patient received 50–100 μg octreotide three times daily subcutaneously for 6 months, resulting in complete resolution of diarrhoea and significant improvement in body weight and quality of life, together with a reduction in VIP concentration to within normal values.ConclusionsAlthough the somatostatin analogue octreotide has been used successfully in the management of both infectious and non-infectious AIDS-related diarrhoea, gastrointestinal neuroendocrine function and circulating humoral mediators of diarrhoea have not hitherto been investigated extensively in HIV-infected subjects. Our data on the association of idiopathic secretory diarrhoea and elevated plasma VIP levels provide a possible pathophysiological rationale for identifying AIDS patients whose refractory diarrhoea may be more responsive to octreotide treatment.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID