摘要:

UNAIDS and WHO produce biannual country-specific estimates of HIV/AIDS and its impact. These estimates are based on methods and assumptions that reflect the best understanding of HIV epidemiology and demography at the time. Where significant advances are made in epidemiological and demographic research, the methods and assumptions must evolve to match these advances. UNAIDS established an Epidemiology Reference Group in 1999 to advise them and other organisations on HIV epidemiology and methods for making estimates and projections of HIV/AIDS. During the meeting of the reference group in 2001, four priority areas were identified where methods and assumptions should be reviewed and perhaps modified: a) models of the HIV epidemic, b) survival of adults with HIV-1 in low and middle income countries, c) survival of children with HIV-1 in low and middle income countries, and d) methods to estimate numbers of AIDS orphans. Research and literature reviews were carried out by Reference Group members and invited specialists, prior to meetings held during 2001-2. Recommendations reflecting the consensus of the meeting participants on the four priority areas were determined at each meeting. These recommendations were followed in UNAIDS and WHO development of country-specific estimates of HIV/AIDS and its impact for end of 2001.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundThe spontaneous in-vitro antibody synthesis observed in unstimulated lymphocyte cultures from HIV-infected patients closely reflects the in-vivo activation of the B cell compartment; however, the mechanisms underlying this phenomenon are far from clear.MethodsWe compared the ability of peripheral blood mononuclear cells (PBMC) and lymph-node cells (LNC) from 10 HIV-infected patients to producein vitroHIV-specific and total Ig spontaneously, and we correlated these parameters with tumour necrosis factor alpha (TNF-α) expression by CD4 T cells, viral dissemination in the organism, and the extent of HIV spread into lymph-node germinal centres, measured by in-situ hybridization (ISH).ResultsIn-vitro spontaneous synthesis of both HIV-specific and total antibody was significantly higher in PBMC than in LNC; the two variables showed a good correlation in LNC, but not in PBMC. In both compartments, no correlation was found between B cell activation and the percentage of CD4 T cells expressing TNF-α, which was increased compared with seronegative donors. Furthermore, no correlation was found between in-vitro spontaneous antibody synthesis and the number of T cells containing proviral HIV in PBMC and LNC, or the plasma levels of HIV RNA. On the contrary, a good correlation was found between HIV-specific B cell activation and the extent of viral spread into lymph-node germinal centres, evaluated by ISH.ConclusionThese data suggest that the adhesion of HIV virions to the follicular dendritic cell network in lymph-node germinal centres may primarily contribute to sustaining the steady B cell activation observed in HIV-infected patients.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo evaluate the virologic responses and mutational profiles in antiretroviral-experienced patients adding tenofovir DF once-daily to their existing regimens.DesignResistance analyses were performed for patients in a phase II placebo-controlled clinical trial of tenofovir DF.MethodsHIV-1 reverse transcriptase and protease genes from plasma samples were analyzed genotypically and phenotypically at baseline, week 24, and week 48.ResultsOf 184 patients, 173 (94%) had baseline HIV-1 expressing one or more nucleoside reverse transcriptase inhibitor-associated resistance mutation. Protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations were observed in 57% and 32% of patients, respectively. Compared to placebo, significant reductions in HIV-1 RNA were observed for tenofovir DF-treated patients who had thymidine analog- (TAM), lamivudine- (M184V), NNRTI- or protease inhibitor-associated mutations. Patients with phenotypic susceptibility to tenofovir within 4-fold of wild-type responded durably to tenofovir DF 300 mg therapy with a decline in plasma HIV-1 RNA of ⩾ 0.5 log10copies/ml; few patients had a more than 4-fold reduced susceptibility to tenofovir at baseline. Four patients (2%) developed the K65R mutation (selected by tenofovirin vitro) and showed 3- to 4-fold reductions in tenofovir susceptibility but no evidence of rebound viremia. Thirty-four percent of patients developed additional TAMs, coincident with concurrent zidovudine or stavudine therapy, but also showed durable HIV-1 reductions. There was no evidence of novel resistance to tenofovir.ConclusionsAdding tenofovir DF 300 mg to an existing regimen in patients with ongoing viral replication and a wide range of genotypic resistance patterns resulted in significant and durable HIV-1 RNA reductions. In addition, there was a low incidence of genotypic or phenotypic resistance to tenofovir DF arising during 48 weeks of therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundThe recently described yeast speciesCandida dubliniensisis closely related toC. albicansand has been recovered predominantly from the oral cavities of HIV-infected individuals and AIDS patients who are often receiving fluconazole as prophylactic or therapeutic treatment for oropharyngeal candidiasis. LikeC. albicans,C. dubliniensissecretes aspartic poteinases which inC. albicanshave been shown to be involved in adherence.ObjectiveTo explain the increasing prevalence ofC. dubliniensisin AIDS patients and to investigate the virulence factors of this yeast.MethodsAnin vitroassay was developed to compare the adherence to epithelial cells ofC. dubliniensisfrom HIV-patients with that ofC. albicans.ResultsAllC. albicansisolates adhered better than the 22C. dubliniensisisolates. In the presence of fluconazole, theC. dubliniensisisolates tested showed increased adherence as compared with controls without fluconazole. In contrast, allC. albicansisolates decreased in adherence to epithelial cells in the presence of fluconazole independently of theirin vitrosusceptibility to this drug. Proteinase antigens are present on the surface ofC. dubliniensiscells adherent to epithelial target cells. In the presence of fluconazole this proteinase antigen was more strongly expressed.ConclusionIncreased adherence ofC. dubliniensisstrains in the presence of fluconazole could explain its high recovery rate from HIV-positive patients in recent years. The induction of proteinase secretion in the presence of fluconazole found for most of theC. dubliniensisisolates could be one of the factors involved in adherence.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveThe mechanisms of HIV-triggered immunodeficiency were examined by determining the segregation of R5 and X4 HIV-1 variants into memory T cell subsets expressing differentially a homing receptor, CD62L-selectin, in human lymphoid tissue.MethodsSubpopulations of CD3 and intracellular p24 gag-positive cells in human lymphoid tissue infectedex vivowith X4 HIV-1 variant NL4-3 and R5 HIV-1 variant AD8 were analysed for expression of the T cell memory markers CD45RO and CD45RA, the T cell homing receptor for lymphoid tissue CD62L, and the HIV-1 coreceptors CCR5 and CXCR4.ResultsMemory CD4 T cells were the predominant targets for productive infection of lymphoid tissueex vivowith both R5 and X4 HIV-1. R5 HIV-1 predominantly infected CD62L-negative memory T cells, which selectively express CCR5. In contrast, X4 HIV-1 variants predominantly infected CD62L+ memory T cells, although CXCR4 coreceptor was equally expressed by memory T cells of both CD62L-positive and CD62L-negative subsets. A high proportion of X4 HIV-1, but not of R5 HIV-1, productively infected T cells, displayed a CD45RA+CD45RO+ phenotype.ConclusionThe selective expression of the CCR5 coreceptor by CD62L-negative terminally differentiated memory T cells correlates with the preferential productive infection of these cells with the R5 HIV-1 variant. The predominance of X4 HIV-1 variants in less-differentiated memory T cells may be related to their recent activation state, as suggested by the coexpression of both CD45RA and CD45RO molecules on their surface. Differential homing of CD62L-positive and CD62L-negative cells suggests different routes of dissemination of X4 and R5 viruses.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivesNatural killer (NK) cell function is likely to be important in controlling HIV infection and opportunistic pathogens. We therefore evaluated NK function and phenotype over the course of antiretroviral therapy (ART) and examined the potential mechanisms of altered NK activity in HIV infection.MethodsWe measured NK cell percentage, NK cytolytic activity (both by flow cytometry) and plasma IL-10 concentrations (by enzyme-linked immunosorbent assay) in 10 HIV-seropositive patients before and over one year of effective ART. To examine potential mechanisms of altered NK activity, we measured NK receptor expression in ART treated and untreated HIV-positive individuals by flow cytometry. As IL-10 enhances NK activity, we studied the effect of IL-10 on NK receptor expression and activity in peripheral blood mononuclear cells (PBMC) from HIV-seronegative individuals.ResultsNK cytolytic activity was elevated in HIV infection and decreased with ART to levels observed in HIV-negative individuals. A greater proportion of NK cells from untreated HIV-positive individuals expressed the NK receptors CD158a and CD161 than either HIV-negative volunteers or effectively treated HIV-positive patients. NK cells from PBMC incubated with IL-10 demonstrated increases in CD158a, CD161 and CD94 expression and increases in cytolytic activity. The treatment-associated decrease in NK activity paralleled a decrease in IL-10 production.ConclusionThe observation that IL-10 alters NK receptor expression similar to that observed in HIV infection, and the fact that NK receptor expression and activity normalize in parallel with ART-induced reduction of circulating IL-10 levels supports a role for IL-10 in NK cell activity and HIV immunopathogenesis.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo evaluate the safety and efficacy of once daily doses of tenofovir DF (TDF) administered in combination with other antiretroviral therapy (ART) in treatment-experienced HIV-1-infected patients with incomplete virological suppression.DesignOne-hundred and eighty-nine subjects with plasma HIV-1 RNA levels between 400 and 100 000 copies/ml and stable ART (⩾ 8 weeks) were randomized (2:2:2:1 ratio) to add TDF 75 mg, 150 mg, or 300 mg or placebo to existing ART in a double-blinded manner. After 24 weeks, patients initially randomized to placebo received blinded TDF 300 mg.MethodsEfficacy was analyzed by the mean changes HIV-1 RNA levels (log10copies/ml plasma; DAVGxx) from week 0 to weeks 4, 24, and 48. Safety was analyzed by incidence of grade 3 or 4 clinical and laboratory adverse events.ResultsAt baseline, patients had mean 4.6 years prior ART use with 94% having HIV-1 with nucleoside-associated resistance mutations. There were statistically significant decreases in DAVG4and DAVG24for all doses of TDF compared with placebo, with the greatest effect seen with TDF 300 mg (DAVG4, −0.62,P< 0.001; DAVG24, −0.58;P< 0.001; DAVG48, −0.62). The incidence of adverse events was similar among the TDF groups and placebo through week 24. Throughout the 48-week study, no significant changes in renal function were observed.ConclusionsIn treatment-experienced patients with baseline nucleoside resistance mutations, TDF provided dose-related, durable reductions in HIV-1 RNA. Through 24 weeks, the safety profile of TDF was similar to that of placebo.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo measure intravertebral bone marrow fat in HIV-infected men.DesignA cross-sectional study of HIV-positive men, subcategorized by lipodystrophy and antiretroviral status, and healthy age- and body mass index (BMI)-matched HIV-negative controls.SettingA tertiary care academic medical institution.PatientsFifteen HIV-infected men and nine age- and BMI-matched healthy control subjects were recruited for bone density, intravertebral bone marrow fat, and body composition measurements.MethodsMagnetic resonance spectroscopy was used to measure intravertebral marrow fat. Quantitative computed tomography was used to quantify visceral and subcutaneous fat. Dual energy X-ray absorptiometry was used to determine lumbar spine bone density. Statistical comparisons were performed according to HIV, lipodystrophy, and protease inhibitor (PI) exposure status.ResultsIntravertebral marrow fat was reduced in HIV-infected men (N = 15) compared with healthy HIV-negative controls (N = 9) (28.5 ± 8.0 versus 37.3 ± 12.5%,P= 0.04). Intravertebral bone marrow fat was most severely reduced in HIV-infected men with lipodystrophy compared with healthy HIV-negative controls (25.6 ± 8.8% versus 37.3 ± 12.5%,P= 0.04). Furthermore, nelfinavir (P= 0.02) was associated with decreased intravertebral marrow fat and indinavir (P< 0.05) was associated with increased intravertebral marrow fat in HIV-infected subjects.ConclusionWe demonstrated reduced intravertebral marrow fat in HIV-infected men using magnetic resonance spectroscopy. Notably, reduced marrow fat occurred in the setting of reduced bone density and may be affected by specific PI and lipodystrophy status. Further studies are necessary to determine the relationship between marrow fat and osteopenia and the effect of antiretroviral therapy on marrow fat in this population.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID