摘要:

Objective:To evaluate serum chemokines, macrophage inflammatory protein (MIP)-1α, MIP-1β and RANTES, concentrations in non-progressing HIV-infected patients and AIDS patients.Setting:University Hospital-based AIDS Clinical Trials Unit.Design/Methods:Serum MIP-1α, MIP-1β and RANTES levels were determined by enzyme-linked immunosorbent assay using archived serum specimens obtained on two occasions at least 1.8 years apart.Patient selection:Long-term non-progressing HIV-infected adult patients were identified from clinic records. For each non-progressing patient, two adult AIDS patients with initial documentation of seropositivity the same year and the same length of follow-up were selected.Results:Four long-term non-progressing patients and eight AIDS patients were studied. Neither the duration of known HIV positivity at the time of specimen collection nor the length of time between specimen collections differed significantly between non-progressing patients and AIDS patients. Serum levels of MIP-1α, MIP-1β and RANTES in specimens obtained either early or later in the course of HIV infection did not differ significantly between non-progressing patients and AIDS patients. In the two patient subsets, significant differences in serum chemokine levels over time were not observed. The rate of change of serum chemokine concentration over time also did not differ between non-progressing patients and AIDS patients. Serum MIP-1α and MIP-1β levels did not reach levels reported to suppress HIV proliferationin vitro. When expressed as a quantity per peripheral blood CD8+ lymphocyte, AIDS patients exhibited significantly greater levels of MIP-1α, MIP-1β and RANTES than non-progressing HIV patients (P< 0.05). These values did not exhibit a significant variation over time.Conclusions:Serum MIP-1α, MIP-1β and RANTES levels do not distinguish patients with AIDS from patients with non-progressing HIV infection. Variations in levels of these chemokines do not explain individual variation in the natural history of HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Objective:To examine risk factors associated with Epstein–Barr virus (EBV) replication in the oral epithelium of an HIV-infected cohort.Design:Longitudinal study of behavioural, medication and immunological parameters of HIV-1-seropositive outpatients attending a genitourinary clinic. Outcome measure was EBV DNA positivity in curetted oral squames, as detected byin situhybridization. Logistic regression for repeated observations of the same individuals was used to analyse how risk changed over time.Results:Fifty six individuals were studied; 158 patient-visits were made in total (mean, 2.8). Of 137 samples curetted from the tongue, 36 were positive for EBV DNA. Recreational drug use, oral sexual practices, therapy with zidovudine and aciclovir, and changes in CD4 and total lymphocyte counts were not associated with changes in risk. Alcohol drinking, elevated CD8 lymphocyte counts and fluconazole therapy were associated with a decreased risk, and cigarette smoking with increased risk.Conclusion:Behavioural and HIV-specific immunological changes may play important roles in promoting and affecting the course of oral EBV replication. Rigorous anticandidal therapy and avoidance of cigarette smoking may retard the development of oral hairy leukoplakia.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Objective:AIDS frequently associates with certain malignancies, including Kaposi's sarcoma, non-Hodgkin's lymphoma (NHL), and anogenital neoplasia. In this study we aimed to define the frequency of infection by human herpesvirus (HHV)-8 throughout the spectrum of AIDS-related neoplasia in Europe.Design:A tumour panel representative of the distinct types of AIDS-related neoplasms was tested for the presence of HHV-8 DNA sequences. Autologous uninvolved tissues were also tested in selected cases.Methods:The presence of HHV-8 DNA sequences was assayed by a combination of polymerase chain reaction followed by oligohybridization and Southern blot hybridization of genomic DNA with an HHV-8-specific probe.Results:HHV-8 sequences were detected in 100% of AIDS-related Kaposi's sarcoma (all 35 cases). Among AIDS-related NHL, HHV-8 sequences selectively clustered with body-cavity-based lymphomas (BCBL; all three cases), although they were consistently negative in small non-cleaved cell lymphomas (none in 18 cases), diffuse large cell lymphomas (none in seven), or anaplastic large cell lymphomas (none in three). No HHV-8 sequences were found in cases of anogenital neoplasia (out of 14) or Hodgkin's disease (out of three). HHV-8 DNA sequences were also positive in the uninvolved skin of all six AIDS-related Kaposi's sarcoma patients, but not in the circulating lymphocytes of a BCBL patient. Positivity for HHV-8 sequences occurred in patients belonging to all major AIDS risk categories.Conclusions:These data confirm that HHV-8 sequences associate at high frequency with selected types of AIDS-related neoplasia, namely Kaposi's sarcoma and BCBL, although they are consistently absent in other types of AIDS-NHL and AIDS-related anogenital neoplasia.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Objective:To assess the diagnostic reliability of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for virus-associated opportunistic diseases of the central nervous system (CNS) in HIV-infected patients.Design:CSF samples from 500 patients with HIV infection and CNS symptoms were examined by PCR. In 219 patients the PCR results were compared with CNS histological findings.Methods:Nested PCR for detection of herpes simplex virus (HSV) type 1 or 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus 6 (HHV-6), and JC virus (JCV) DNA. Histopathological examination of CNS tissue obtained at autopsy or on brain biopsy.Results:DNA of one or more viruses was found in CSF in 181 out of 500 patients (36%; HSV-1 2%, HSV-2 1%, VZV 3%, CMV 16%, EBV 12%, HHV-6 2%, and JCV 9%). Among the 219 patients with histological CNS examination, HSV-1 or 2 was detected in CSF in all six patients (100%) with HSV infection of the CNS, CMV in 37 out of 45 (82%) with CMV infection of the CNS, EBV in 35 out of 36 (97%) with primary CNS lymphoma, JCV in 28 out of 39 (72%) with progressive multifocal leukoencephalopathy. Furthermore, HSV-1 was found in one, VZV in four, CMV in three, EBV in three, HHV-6 in seven, and JCV in one patient without histological evidence of the corresponding CNS disease.Conclusions:CSF PCR has great relevance for diagnosis of virus-related opportunistic CNS diseases in HIV-infected patients as demonstrated by its high sensitivity, specificity, and the frequency of positive findings.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Objective:To identify appropriate criteria for characterizing HIV-infected nonprogressors.Design:Five definitions were compared as follows: (1) last CD4 count > 500×106/l; (2) two most recent CD4 counts > 500×106/l; (3) calculated CD4 count based on linear regression > 500×106/l; (4) CD4 slope ≥ 0 with no antiretroviral use; (5) all CD4 counts > 500×106/l, decline in CD4 slope < 5 cells per year, no antiretroviral use.Participants:Five prospective cohorts of homosexual men with documented dates of HIV-1 seroconversion.Main outcome measures:Proportions of nonprogressors were calculated 7, 8, 9 and 10 years following seroconversion (n = 285). Definitions were evaluated with respect to consistency over time and across sites. Subjects lacking CD4 counts within 3 years preceding end of follow-up were excluded.Results:Across sites, proportions of nonprogressors ranged from 1% (definition 5) to 17.5% (definition 1) 10 years after seroconversion. Definitions based on absolute CD4 counts (definitions 1–3) had higher proportions and were less consistent than those based on stable slopes (definitions 4 and 5). For each definition, proportions decreased as follow-up increased, but were most stable for definition 4 (3%). Site differences decreased as follow-up increased, but remained nearly threefold for definitions 1–3. None of the definitions classified the same subjects as nonprogressors at any timepoint.Conclusions:Observations regarding nonprogression are highly dependent on the definition and the duration of follow-up. Our findings highlight methodological challenges which will need to be overcome in natural history studies of nonprogression.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Objective:Several small short-term intervention studies have suggested that β-carotene supplementation in HIV-infected patients can increase the number of various immune cells including CD4 cells. This prospective double-blinded study was designed to investigate whether β-carotene supplementation would result in this immuno-enhancement in a larger number of patients over a longer time period.Methods:HIV-positive patients were randomly assigned to receive either 60 mg β-carotene orally three times daily or a matched placebo. In addition, all patients received a multivitamin supplement. Patients were evaluated at baseline, 1 month, and 3 months for T-cell quantitative subsets, natural killer cells, HIV p24 antigen, β-carotene levels, complete blood counts and chemistry batteries. Body weights and Karnofsky scores were evaluated at each visit.Results:Seventy-two patients signed informed consent forms and entered the study. Except for serum β-carotene concentration, there were no statistically significant differences (P< 0.05) between the treatment (60 mg β-carotene three times daily and multivitamins) and placebo (placebo and multivitamins) groups at baseline or after either 1 or 3 months of treatment.Discussion:Earlier studies suggesting that β-carotene supplementation increased levels of immune cells in HIV-infected patients were not replicated in this study. The addition of a multivitamin supplement to both arms of this study may have masked any difference between the two groups. However, on the basis of the results of this study, we would not recommend supplementation with high doses of β-carotene for HIV-infected patients.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Objective:To study the effect of HIV-1 resistance to lamivudine (3TC) and zidovudine (ZDV), and syncytium-inducing (SI) phenotype on virologic response to treatment with ZDV, 3TC, or ZDV plus 3TC in previously untreated individuals with HIV-1 infection.Design:A prospective virologic substudy of GlaxoWellcome protocol NUCA 3001.Methods:HIV-1 isolates obtained at study entry and at week 12 were expanded in peripheral blood mononuclear cell (PBMC) culture, titered, and assayed for phenotypic and genotypic evidence of resistance to ZDV and 3TC, and for syncytium formation on MT-2 cells.Results:Phenotypic and genotypic resistance to 3TC was detected in the majority of HIV-1 isolates from patients who received 3TC alone or in combination with ZDV. Despite showing 3TC resistance, subjects who received 3TC in combination with ZDV had significantly greater decreases in plasma HIV-1 RNA levels compared with those who received ZDV alone. Occurrence of the K70R ZDV resistance mutation was significantly reduced in patients who received the 3TC/ZDV combination as compared with patients on ZDV monotherapy. Plasma HIV-1 RNA returned to near-baseline levels more quickly in patients with SI isolates at study entry.Conclusions:Despite the rapid emergence of 3TC resistance, combination therapy with 3TC plus ZDV resulted in greater reduction in plasma HIV-1 RNA levels over 24 weeks as compared to ZDV monotherapy. Prevention of ZDV resistance may contribute to the sustained activity of the combination therapy.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Objective:In HIV-infected patients there is an increased frequency of fungal infections. Dysregulation of the response of phagocytic cells to fungal pathogens may be involved.Design:Phagocytosis ofCandidaspp., consecutive intracellular production of reactive oxygen species, and candicidal activity were analysed in polymorphonuclear leukocytes (PML) from HIV-1 -infected patients, who were at stage C3 of the 1993 revised Centers for Disease Control and Prevention classification system, by means of flow cytometry.Methods:Phagocytic ability was assessed by measuring uptake of fluorescein isothiocyanate-labelledCandida albicans, C. KruseiandC. glabrata. Reactive oxygen intermediate production was estimated by the quantity of dihydrorhodamine-123 converted to rhodamine-123 intracellularly. The candicidal effect was assessed by the propidium iodide uptake of killed yeast cells.Results:As compared to PML of healthy, HIV-negative controls, PML of AIDS patients exhibited an increased phagocytic activity and a similar ability to generate reactive oxygen products. In contrast, PML of AIDS patients displayed a decreased candicidal activity (P< 0.05 compared to controls).Conclusion:These results suggest that in patients with advanced HIV-1 infection the impairment of non-oxidative killing mechanisms of phagocytic cells may contribute to the high incidence of fungal infections.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Objective:HIV-related gastrointestinal infection is associated with diarrhoea, weight loss, mucosal inflammation and increased intestinal permeability. As tumour necrosis factor (TNF)-α may mediate these features this cytokine was measured in the faeces of HIV-seropositive individuals with diarrhoea to assess its role in the pathogenesis of HIV-related gastrointestinal disease and the association with specific intestinal pathogens.Design:Prospective study.Methods:Two hundred and four HIV-seropositive individuals provided stool samples that were analysed for faecal TNF-α (FTNF-α) using a standard sandwich enzyme-linked immunosorbent assay.Results:Stool from patients with bacterial, cytomegalovirus (CMV) and microsporidial diarrhoea had significantly elevated FTNF-α compared with those who had pathogen-negative diarrhoea (P< 0.05). FTNF-α was not raised in cryptosporidiosis, pathogen-negative or solid stool. In subjects with diarrhoea of more than 2 weeks duration and three stool samples negative for enteric pathogens, FTNF-α greater than 15 U/ml has a sensitivity of 88% and a specificity of 66% for the diagnosis of diarrhoea-related CMV enteritis.Conclusion:TNF-α production may have a role in the pathogenesis of bacterial, microsporidial and CMV-related diarrhoea in HIV-seropositive individuals. Thus, anti-TNF-α agents may have a therapeutic role in the management of these conditions. FTNF-α greater than 15 U/ml in apparently pathogen-negative diarrhoea may suggest endoscopic gastrointestinal biopsy to diagnose CMV enteritis.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Objective:To define genotypic and phenotypic resistance patterns following prolonged therapy with the protease inhibitor ritonavir (ABT-538).Design:Seven HIV-1-infected patients, all but one previously treated with dideoxynucleoside analogues (zidovudine, didanosine, zalcitabine), were treated for 1 year with ritonavir.Methods:Direct solid-phase sequencing of the protease gene starting from plasma derived viral RNA followed by comparison to phenotypic drug resistance data.Results:The most frequent amino-acid substitutions occurring upon administration of the protease inhibitor were V82A/F (substrate binding site), I54V (flap region), A71V and L10I. Additional mutations found in more than one patient were I15V, M36I, I84V and I93L. Mutation L63P was found both in pre- and post-ritonavir samples. Phenotypic drug resistance assays confirmed resistance to ritonavir in post-treatment samples (~170-fold) and showed cross-resistance to indinavir (~30-fold) and partially to saquinavir (~fivefold). At 1 year of treatment, one patient without known resistance-associated mutations in the protease gene still showed a substantial rise in CD4 cell count accompanied by a more than 2.4 log decrease in RNA viral load. However, at week 78, mutations R8Q, E34K, R57K, L63P and I84V were detected and the treatment benefit was partially lost.Conclusions:Long-term treatment with ritonavir is associated with the emergence of multiple mutations in the HIV-1 protease gene. The mutations L10I, I54V, L63P, A71V, V82A/F and I84V correspond to known drug-resistance mutations for ritonavir and other protease inhibitors. Phenotypic resistance to ritonavir was detected in a majority of ritonavir-treated patients at 1 year of treatment. In addition, long-term ritonavir treatment selects for cross-resistance to the protease inhibitors indinavir and saquinavir. This argues against sequential therapy with several protease inhibitors. Delayed resistance in one patient was accompanied with a prolonged increase in CD4 cell count and decrease in viral load suggesting a temporary benefit of treatment.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID