ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundTuberculosis is a leading cause worldwide of morbidity and mortality among HIV-infected people. The HIV era has seen a dramatic increase of the tuberculosis case fatality rate (CFR) in high HIV prevalence populations. Providing care for HIV-infected people must include measures to tackle this high tuberculosis CFR.AimsTo analyse the extent of the increased tuberculosis CFR in high HIV prevalence populations in sub-Saharan Africa, the reasons for this increase and the causes of death, in order to identify possible ways of tackling this problem.MethodsReferences were obtained by searching the MEDLINE on ‘tuberculosis', ‘HIV infection', and ‘mortality’ (MesH or textword). In addition, available data from National Tuberculosis Programme reports were reviewed.FindingsTuberculosis CFR is closely linked to HIV prevalence. Limited autopsy data suggest that death from HIV-related diseases other than tuberculosis is probably the main reason for the increased CFR in HIV-infected tuberculosis patients. Among HIV-infected tuberculosis patients, the higher tuberculosis CFR in sputum smear-negative and extrapulmonary than in sputum smear-positive tuberculosis cases can also be attributed to misdiagnosis of HIV-related diseases as tuberculosis. The adverse effect of the HIV/AIDS epidemic on general health service performance probably accounts for the higher tuberculosis CFR among HIV-negative tuberculosis patients in high prevalence populations than that in low HIV-prevalence populations.ConclusionTackling the problem of the increased tuberculosis CFR in high HIV prevalence populations requires collaboration between tuberculosis control and HIV/AIDS programmes in implementing measures such as improved health services, tuberculosis and HIV control services, preventive treatment for HIV-related diseases and anti-HIV treatment.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesLymphoid tissue is a major reservoir for virus replication in HIV-infected subjects. The relationship of CCR5 and CXCR4 coreceptor density and HIV replication in peripheral blood mononuclear cells (PBMC) and lymph node (LN) mononuclear cells (LNMC) of HIV-infected subjects was examined.MethodsPBMC and cervical LNMC from 12 HIV-infected patients were examined for virological and immunological parameters including chemokine receptor density, HIV plasma and cellular viral load, coreceptor usage and CD38/HLA-DR expression.ResultsThe number of CCR5 and CXCR4 molecules on CD4 lymphocytes in the LN were significantly higher than in PBMC. In contrast the number of CD4 molecules/CD4 T cell was higher in PBMC than in LNMC. The CXCR4/CD4 and CCR5/CD4 ratios in the LN were significantly higher than in the PBMC. This was associated with a cellular viral load in the LN that was ~110-fold higher than in PBMC. The absolute number of coreceptor molecules per cell did not correlate with the viral load. However, the CCR5/CD4 and CXCR4/CD4 ratios in the LN positively correlated with HIV cellular and plasma RNA. Characterization of the viral isolates suggested an association between clinical isolates using a distinct coreceptor and the upregulation of the corresponding chemokine receptor.ConclusionsThe ratios of chemokine receptors to CD4 molecules in CD4 T cells from LN is higher than in PBMC and may account for the relative difference in cellular viral load in these compartments. Additionally, the coreceptor/CD4 ratios, particularly in the lymphoid tissue, were highly related to HIV replication.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundMost mutations detected for the gene for CC chemokine receptor 5 (CCR5) are either relatively specific to different population groups or rarely observed in Africans.ObjectivesTo develop a comprehensive mutation detection assay for the entire coding region ofCCR5and to identify novel mutations that may play a role in genetic susceptibility to HIV-1 infection, within the diverse South African population.DesignThe study cohort consisted of 103 HIV-seropositive patients and 146 HIV-seronegative controls of predominantly African descent.MethodsA mutation detection assay for the entire coding region ofCCR5was designed; this included amplification of part of the coding region ofCCR2. The assay was based on denaturing gradient gel electrophoresis (DGGE) and allowed the complete analysis of samples from 10 individuals per denaturing gel.ResultsThe use of theCCR5-DGGE assay led to the identification of seven novel and six previously reported mutations. All novel mutations, including a common polymorphism at codon 35, occurred exclusively in non-Caucasians, indicating possible African origin.ConclusionA comprehensive DGGE mutation detection assay has been developed for the entire coding region ofCCR5. Application of this assay resulted in the identification of novelCCR5mutations, which may have a significant effect on the normal functioning of CCR5 and thus contribute to host variability and susceptibility to HIV-1 infection and/or progression to AIDS within this population.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo evaluate CD4 T-cell cytopathicity of protease inhibitor (PI)-resistant isolates from patients with preserved CD4 cell counts after long-term virologic failure.MethodsPI-resistant primary isolates from 14 patients with stable or increasing CD4 T-cell counts despite long-term virologic failure during continuous combination therapy were examined. Replication and cytopathicity were assessed in activated peripheral blood mononuclear cell cultures in the presence and absence of PI using titered stocks of primary HIV-1 isolates and during initial viral isolation. Also studied were PI-sensitive isolates from four of these patients after therapy discontinuation and reversion to PI-sensitive virus and from seven antiretroviral drug-naive patients. Coreceptor use, syncytia-inducing (SI) phenotype and protease sequences were determined by standard methods.ResultsAll isolates obtained during continued therapy showed genetic markers of PI resistance and decreased phenotypic susceptibility. PI-resistant SI isolates were highly to moderately cytopathic whereas non-syncytia-inducing isolates were moderately to weakly cytopathic. PI-susceptible and PI-resistant isolates obtained after discontinuation of therapy were equally cytopathic at similar replication levels. The cytopathicity of PI-resistant isolates was not altered by PI and was similar to that of isolates from untreated subjects.ConclusionsPrimary isolates from patients showing virologic rebound without net CD4 T-cell loss during continued therapy are as cytopathic as PI-sensitive isolates with equivalent input infectious titer. As with PI-sensitive isolates, cytopathicity of PI-resistant viruses was determined primarily by coreceptor preference. These results suggest that the sustained immunologic response observed after failure of PI-containing regimens is not due to the emergence of PI-resistant strains that are intrinsically less cytopathic for activated peripheral CD4 lymphocytes.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic.SubjectsA total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC).ResultsThe median CD4 count at starting HAART was 171 × 106cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years;P= 0.0008], as were previously treatment-naive patients (RH, 0.65;P= 0.0050), those in a clinical trial (RH, 0.64;P= 0.027) and those who started nelfinavir (RH, 0.57;P= 0.035). Patients who started with four or more drugs (RH, 2.21,P< 0.0001), who included ritonavir in the initial regimen (RH, 1.41;P= 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51;P< 0.0001) were more likely to modify HAART.ConclusionsThere was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo examine the impact of highly active antiretroviral therapy (HAART) on the outcome of HIV-1-related cognitive impairments using a neuropsychological (NP) battery to assess separately the psychomotor, executive function and memory fields.DesignA longitudinal study of HIV-1-infected patients based on serial NP tests in a Paris University Hospital.MethodsA group of 91 HIV-1-infected patients, of whom 47 were already taking HAART at their first NP examination, were initially categorized as cognitively impaired (n = 53) or non-impaired (n = 38) and underwent one to six serial NP batteries (mean follow-up 12.3 ± 8.3 months). Generalized estimating equations (GEE) were used to evaluate performance in a given NP test according to the number of days on HAART.ResultsDespite a 25% mortality rate among patients who had cognitive impairment at their first NP examination, GEE showed a positive relationship between the duration of HAART and cognitive performance. Performance in psychomotor tests (e.g. Purdue Pegboard dominant hand) improved continuously during the study period, while memory test performance (e.g. Grober and Buschke free recall) tended to reach a plateau.ConclusionsHAART improves subcortical cognitive functions during the first year of treatment. Distinct neuropathological mechanisms appear to underlie psychomotor and memory dysfunctions in AIDS.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo describe the use of second line protease-inhibitor (PI) regimens across Europe and to determine factors associated with virological and immunological response.DesignAnalysis of data from 984 patients with a median follow-up of 21 months enrolled in EuroSIDA. Patients started their second PI-containing regimen at least 16 weeks after starting the first PI-containing regimen and with viral load > 1000 copies/ml.MethodsVirological response was defined as a viral load < 500 copies/ml and immunological response as an increase of 50 × 106/l or more in CD4 lymphocyte count.ResultsThe median CD4 cell count at starting the second PI was 171 × 106cells/l; viral load was 4.45 log copies/ml. As a second PI regimen, 45% were using a dual PI, while of those on one PI, indinavir (42%) and nelfinavir (34%) were most common. In multivariate Cox models, a higher viral load at starting the second PI [relative hazard (RH), 0.67 per 1 log higher; 95% confidence interval (CI), 0.58–0.77;P< 0.0001) and a lower CD4 cell count (RH, 1.15 per 50% higher; 95% CI, 1.06–1.26;P= 0.0014) were associated with a reduced probability of virological response. Those who had achieved viral suppression on the first PI-regimen were more likely to respond to the second (RH, 1.65; 95% CI, 1.30–2.10;P< 0.0001) as were those who added one or two new nucleosides to their second PI.ConclusionsPatients who initiate a second PI regimen at lower viral load, higher CD4 cell count or who added new nucleosides tended to be more likely to achieve a viral load < 500 copies/ml. The roles of cross-resistance and adherence in response to second-line regimens needs further investigation.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo describe clinical experience with atovaquone suspension for the treatment ofPneumocystis cariniipneumonia (PCP) in HIV-infected patients.DesignA retrospective chart review.MethodsThe medical records of 54 HIV-infected patients with PCP treated with atovaquone were examined. The outcomes of 34 patients treated with atovaquone suspension (750 mg twice a day) were compared with those of 20 patients treated with atovaquone tablets (750 mg three times a day).ResultsThe proportion of patients successfully treated was similar with the suspension (74%) and tablet (70%) formulations of atovaquone. The proportion of patients with an inadequate response to therapy was lower for patients treated with atovaquone suspension (15%) than tablets (30%). Both formulations were well tolerated.ConclusionAtovaquone suspension is effective and well tolerated for the treatment of PCP.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID