ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Since the early 1990s, colposcopy of the vagina and cervix has been used in the development of vaginal products in order to detect epithelial changes that may increase the likelihood of HIV or acquisition of other sexually transmitted diseases. As part of a continued effort to examine and define the role of colposcopy in a research setting, the Contraceptive Research and Development Program (CONRAD) and the International Working Group on Microbicides (IWGM), in association with the United Nations Program for AIDS (UNAIDS) sponsored a conference entitled, ‘The Use of Colposcopy in Assessing Vaginal Irritation in Research', held in Washington, DC in January 1999. This is a report of that conference.The World Health Organization's colposcopy procedure and nomenclature, published in 1995, were reviewed and changes were recommended. The revised procedure involves colposcopic examination of the external genitalia, naked eye examination of the cervix, fornices, and vaginal walls, followed by lavage and colposcopic examination of those areas, and sampling as appropriate for microscopic examination. Revised nomenclature replaces the terms used for findings with descriptions of what is actually seen. Digital video imaging and testing for inflammatory markers may be adjuncts to colposcopy and should be further studied. Other areas requiring additional research include the natural history of colposcopic changes, factors other than product use that may affect colposcopic findings, the clinical significance of findings, and the procedure which best assesses these findings.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo examine the influence of change in antiretroviral therapy (ART) on patterns of CD8 T cell clonal dominance in HIV-infected children.DesignSeventeen HIV-infected children with plasma virus loads between 3.1 and 5.7 log10were investigated before and after changes in ART.MethodsCDR3 spectratyping was performed in 22 T cell receptor (TCR) Vβ subfamilies by multiplex polymerase chain reaction (PCR) in purified peripheral blood CD8 T cells in conjunction with CD4 cell counts, plasma HIV-RNA copies and lymphoproliferative assays (LPA).ResultsCD8 T cell clonal dominance in two or more Vβ families was present in eight out of 17 children. After a change in therapy, 13 patients (76%) acquired new clones whereas three patients (17.6%) showed a loss in CD8 cell clones. An increase in the numbers of dominant clones correlated with an increase in percentage CD4 cell counts (P< 0.001) and with improved LPA responses to tetanus (P< 0.05) and alloantigens (P< 0.01). CD4 cell increase was associated with an initial mean gain of 3.1 ± 2.1 CD8 cell clones, independent of a virological response. A loss of CD8 cell clones or failure to achieve CD4 T cell increase was associated with failure to achieve virological suppression.ConclusionChildren with chronic HIV infection manifest CD8 T cell clonal dominance, which appears to be dependent upon the adequacy of the CD4 cells. With optimization of therapy, a gain in clonal dominance is the predominant response, except in situations of failure to contain viral replication.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo characterize immune phenotype and function in hepatitis C virus (HCV) infection in the presence and absence of HIV-1 infection.DesignCross-sectional comparison among controls (group A), patients with HCV infection (group B), HCV–HIV-1 coinfected patients (group C), coinfected patients receiving treatment for HIV-1 (group D), and untreated HIV-1 infected patients (group E).MethodsFlow cytometric analysis for lymphocyte phenotypes, lymphocyte proliferation and cytokine production by ELISPOT.ResultsHCV infected patients tended to have an increased percentage of activated (CD38, HLA-DR) CD8 cells (group A, 2 ± 1.4%; group B, 6 ± 3.9%;P= 0.08). Proliferative responses to non-HCV antigens were comparable in group A and group B subjects. A greater proportion of group B patients had stimulation indices (SI) > 3 to the HCV protein NS3 compared to group C and D patients (67%, 0%, and 11% respectively;P< 0.003), but only two patients in group B had SI ⩾ 5. The SI to NS3 was significantly higher in group B patients [median, 4; interquartile range (IQR), 3–9) than in group C (median, 2; IQR, 1–3;P< 0.04) or group D (median, 1; IQR, 1–4;P< 0.009) patients. Plasma HCV RNA levels correlated directly with alanine aminotransferase levels (ρ, 0.52;P< 0.05) and inversely with the number of CD4 lymphocytes (ρ, −0.55;P< 0.009) and proliferation to NS3 (ρ, −0.55;P< 0.009).ConclusionsLymphocytes of HCV infected patients show weak proliferative responses to HCV antigens while responses to other antigens are preserved. Infection with HIV-1 potentiates this deficiency. Poor CD4 T cell responses to HCV are associated with and may determine the failure to control HCV propagation.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo investigate the changes in genotypic drug-resistance pattern, plasma HIV RNA and CD4 cell count after treatment interruption and assess the short-term antiviral effect of a new salvage regimen.DesignProspective study of 38 patients with multiple failing regimens who had completely stopped all medication for 3 months before a three to five-drug regimen was reintroduced according to clinical guidelines.MethodsPatients were tested for HIV resistance before and after treatment interruption by population-based sequencing and clonal analysis of selected patients.ResultsDiscontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 0.4 log10and a median decrease in CD4 cell count of 43 × 106/l. Sixty-one per cent of patients had a shift from the drug-resistant genotype to a predominantly wild-type genotype. The patients significantly likely to show genotype reversion were those in Centers for Disease Control groups A or B, who had been exposed to few drugs, had a low plasma HIV RNA, or a high CD4 cell count. The only independent factor predicting genotype reversion was the clinical stage. The median change in plasma HIV RNA at month 3 after treatment reintroduction was −2.3 log10copies/ml in patients who had genotype reversion compared with −0.6 log10copies/ml in patients without genotype reversion (P= 0.004).ConclusionSuspending treatment for 3 months after multiple failures could be a suitable strategy for optimizing salvage therapy provided it is instituted early, before the HIV disease becomes too advanced.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveWhen to start highly active antiretroviral therapy (HAART) in asymptomatic chronically HIV-1-infected subjects with CD4 cell counts of 300 × 106–500 × 106/l is debated extensively. Retrospective analyses of virological and immunological responses following HAART have been evaluated in both blood and lymph nodes according to pre-treatment levels of CD4 cells either above or below 500 × 106/l.DesignOpen-label, observational, non-randomized, prospective study.SettingOutpatients attending the Centre of Clinical Investigation in Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland.ParticipantsFifty-four HIV-1-infected antiretroviral-naive subjects with CD4 cell count ⩾ 250 × 106/l and plasma viraemia ⩾ 5000 copies/ml who had been treated with HAART for at least 48 weeks. Controls were 49 HIV-negative subjects.InterventionsAll patients received abacavir, nelfinavir, saquinavir soft gel capsules, and amprenavir in varying combinations for 72 weeks.Main outcome measuresThe extent of immune reconstitution following HAART in 43 and 11 subjects with either more or fewer than 500 × 106CD4 cells/l at baseline was evaluated in blood and lymph node, and compared with immunological measures observed in 49 HIV-negative controls.ResultsAfter 48 weeks of therapy, plasma viraemia was suppressed effectively in both groups of patients. Normalization of both CD4 cell count in blood, divided equally between memory and naive cells, and percentage of CD4 cells in lymph nodes occurred in the two groups. Consistently, the net increase over baseline in CD4 cell count and in memory and naive CD4 subsets was greater in patients with fewer than 500 × 106CD4 cells/l at baseline. Recovery of HIV-specific responses was similar in the two groups.ConclusionsThis study suggests that virological and immunological responses are comparable in asymptomatic therapy-naive HIV-1-infected subjects with CD4 cell counts above or below 500 × 106/l.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo perform molecular analysis of the predominant viral populations and drug-resistance mutations from plasma and peripheral blood mononuclear cell (PBMC) compartments over time from an HIV infected patient, who experienced virological failure while on different HAART regimens.Materials and methodsIn a longitudinal study proviral and plasma HIV-1 sequences were amplified in thepol, protease andenvgenes and were sequenced directly and analysed phylogenetically. Virus was recovered from time points corresponding to viral load peaks using co-culturing techniques. The periodic failure of different highly active antiretroviral therapy (HAART) regimens was analysed sequencing.ResultsLongitudinal follow-up studies revealed four inflection peaks of plasma viraemia associated with the recovery of culturable virusin vitro, which indicated failure of the concurrent HAART regimen.Molecular analysis of viral strains revealed evidence of continual evolution and compartmentalization of drug-resistance mutants/quasispecies between plasma and PBMC, with the widest spectrum of mutations isolated from plasma. Importantly, these data show the periodic appearance and clearance of drug-resistance mutants concomitant with the introduction and withdrawal of zidovudine over time.ConclusionThis report is unique in showing drug-induced compartmentalization of viral quasispecies under the control of different HAART regimens in both plasma and PBMC. Introduction and withdrawal of zidovudine from the HAART regimen had direct bearing on the appearance and disappearance of specific zidovudine drug-resistance mutations in plasma-derived virus. This data has important implications for the management of HIV-infected patients with poor compliance with certain HAART regimens, and also in predicting the late emergence of drug-resistance mutationsviathe latent integrated provirus.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo determine the overall distribution of drug-resistance mutations to nucleoside reverse transcriptase inhibitors of HIV strains recovered from the lymph nodes (LN) and peripheral blood mononuclear cell (PBMC) compartments of four HIV-infected patients receiving zidovudine and didianosine and to compare them with antiretroviral-naive patients.DesignMolecular comparison of major and minor HIV-1envandpolregion variants residing in LN and PBMC compartments.Materials and methodsProviral DNA sequences were amplified by PCR from both PBMC and LN compartments, cloned into PGEM-T II Easy vector and sequenced. The clones were subjected to molecular and phylogenetic ananlysis.ResultsComparison of PBMC and LN-derived HIV-1 variants in theenvV3 region showed that nucleotide and amino acid variability was a characteristic feature of LN-derived variants. In contrast, a majority of resistance mutations to reverse transcriptase inhibitors were localized in the PBMC compartment rather than in LN, which is thought to be a reservoir of HIV.ConclusionsDistinct compartmentalization or independent evolution ofpolandenvgene variants between LN and PBMC could be due to the differential selection pressure imposed by the combination drug regimen, hence the bimodal distribution of resistance variants between LN and PBMC compartments.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo study the natural course of viremia during primary HIV infection (PHI).MethodEight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-1 RNA levels were measured frequently and the results were fitted to mathematical models. HIV-1 RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness.ResultsHIV-1 RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-1 RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/ml.ConclusionsThis study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-1 infection: PHI peak levels correlate with steady-state levels and HIV-1 RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo quantify unbound indinavir concentrations and characterize indinavir plasma protein binding in HIV-infected adults.DesignPharmacokinetic study in antiretroviral-naive, HIV-infected persons with CD4 T lymphocytes > 100 × 106cells/l and HIV-RNA in plasma > 5000 copies/ml at baseline who were participating in an open-label study of zidovudine, lamivudine and indinavir therapy.MethodsEight men underwent 8 h intensive pharmacokinetic studies for indinavir on two occasions 6 months apart. Unbound indinavir was separated by ultra-filtration, and unbound and total concentrations were quantified by a validated high-performance liquid chromatography method.ResultsOverall indinavir protein binding was 61 ± 6%, with a range among the profiles of 54 to 70%. Indinavir binding was higher at the 8 h post-dose concentration compared with the 1 h post-dose concentration (66 versus 57%,P= 0.0006).ConclusionsThe mean 61% protein binding for indinavir in these HIV-infected persons is similar to thein vitroreport of 60%. However, the fraction bound was concentration-dependent, and considerable variability in binding was present among patients. Quantification of unbound protease inhibitor concentrations opens new avenues of research to advance our understanding of the pharmacologically-relevant moieties of antiretroviral agents and thereby the pharmacotherapy of HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID