ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectivesTo examine the genetic variation of HIV-1 isolates in Abidjan, Côte d'lvoire, and to determine the extent to which phylogenetic trees based on sequence information of part of theenvgene containing the principal neutralizing domain are representative for documenting genetic variability.DesignPhylogenetic comparison of 13 HIV-1 strains isolated from patients in Abidjan with previously documented HIV-1 strains of different geographic origin.MethodsTo sequence a 900 base-pair fragment of theenvgene containing V3, V4, V5 and the beginning of gp41 of three to four clones per isolate. Phylogenetic tree analysis was performed with the software package TREECON.ResultsEleven HIV-1 isolates of Abidjan were classified as genotype A, while two were classed as genotypes B and D. Intra-genotype A distances at the nucleotide level were a maximum of 14.1%. Inter-genotype distances between genotype A and genotypes B, C, and D varied from 16.0 to 22.6%. Phylogenetic trees, based on sequence data of a 300 base-pair fragment containing the V3 loop, showed significant differences in tree topology and statistical confidence with phylogenetic trees based on sequence data of the 900 base-pairenvfragment.ConclusionsGenotype A Côte d'lvoire HIV-1 strains, which comprise 11 out of 13 isolates, predominate in Abidjan, which may indicate a local burst of particular variants. Phylogenetic trees should be interpreted with caution when based on a more limited number of nucleotides, such as the V3 region.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo measure changes in HIV-1 virus load following zidovudine therapy, and to investigate the relationship between these changes and clinical progression.DesignProspective study of 18 symptomatic, zidovudine-naive patients, with CD4 count < 350x106/l.MethodsThe following parameters were measured at each visit, before zidovudine therapy, after 1 month of therapy, and every 3 months thereafter. HIV-1 virus load in peripheral blood was determined by serum immune complex-dissociated HIV-1 p24antigen (ICD-p24Ag), quantitative plasma and cellular viraemia. A virologic response under zidovudine was defined as >50% decrease in ICD-p24Ag levels or > 1 log10decrease in plasma or cellular viraemia litres from baseline values. CD4 and CD8 cell counts, and β2-microglobulin levels were also measured. Disease progression was defined as the time to a new AIDS-defining event or death.ResultsAt enrolment, 13 out of 18 (72%) patients had positive ICD-p24Ag and positive plasma viraemia, with a mean of 44 median tissue culture infective dose (TCID50per ml; all patients had positive cellular viraemia with a mean TCID50of 230 per 106/l cells. Median CD4 cell count was 43 x 106/l. Ten patients developed a new AIDS-defining event and eight died during a median follow-up of 15 months on zidovudine. Baseline prognostic markers for development of a new AIDS-defining event included ICD-p24Ag, CD4 and CD8 cell counts, but only CD4 cell count remained predictive on multivariate analysis (P= 0.003). When each laboratory marker was analysed as a time-dependent covariate, only CD4 (P= 0.002) and CD8 (P= 0.001) cell counts predicted the occurrence of a new AIDS-defining event. Eight out of 13 (61.5%) patients had an ICD-p24Ag response, and seven out of 13 (54%) a plasma viraemia response, but only cellular viraemia responders (five out of 18; 28%) had a 5.6-fold decrease in their risk of developing an AIDS-defining event (90% confidence interval, 1–33;P= 0.05) None of these markers correlated with survival.ConclusionsPlasma viraemia and ICD-p24Ag, while providing useful short-term markers of zidovudine antiviral activityin vivo, do not correlate with disease progression in patients with advanced HIV infection. CD4 cell count remained the best initial and time-dependent predictor for development of new AIDS-defining events. Interestingly, a high CD8 cell count and a decrease in cellular viraemia litres also appear to be predictive of improved clinical outcome in this population.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveDescription of the relationship between repeated measurements of CD4 lymphocyte count and development of AIDS in asymptomatic HIV-infected patients.DesignRepeated measurements of CD4 lymphocyte counts over an AIDS-free period in asymptomatic HIV-infected patients, and follow-up of the cohort to record subsequent clinical progression to AIDS.MethodsThe cohort was studied in a double-blind randomized clinical trial. CD4 lymphocyte counts were measured on three occasions over 8 months in 851 patients.ResultsEighty subsequent clinical progressions to AIDS were recorded during a median follow-up period of 15.3 months. Each of the three measurements of CD4 lymphocyte count were separately predictive of subsequent progression to AIDS. However, when the three measurements were included simultaneously in a predictive model only the last measurement showed a significant predictive value. Change in individual CD4 count was also related to the risk of developing AIDS, but was no longer significant when the most recent measurement was included in the model.ConclusionThese results indicate the closeness of the relationship between the actual state of the immune system and subsequent progression to AIDS.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo determine whether the anti-angiogenesis agent DS-4152 inhibits the replication of HIV-1in vitro.DesignA sulfated polysaccharide-peptidoglycan DS-4152 has recently been identified as a potent and selective inhibitor of Kaposi's sarcoma (KS). Therefore, it is important to evaluate the anti-HIV-1 activity of DS-4152 alone and in combination with dideoxynucleosides.MethodsActivity of DS-4152 against HIV-1 replication was examined in MT-4, Molt-4, and peripheral blood lymphocyte cells. The inhibitory effect of the compound on syncytium-formation was determined by cocultivation of Molt-4 cells with Molt-4/IIIbcells. Inhibition of virus adsorption to the host cells was measured by a p24antigen capture enzyme-linked immunosorbent assay.ResultsDS-4152 showed potent and selective inhibition of HIV-1 replication in the cell systems. Its 50% effective concentration for HIV-1 (IIIBstrain) in MT-4 cells was 0.7μg/ml. The compound was not cytoxic at concentrations ≤ 100 μg/ml. DS-4125 proved inhibitory to syncytium-formation and virus adsorption. The anti-HIV-1 activities of zidovudine, dideoxycytidine and dideoxyinosine were not affected by the presence of DS-4152.ConclusionDS-4152 has the potential, from thesein vitrostudies, to function as an anti-HIV-1 as well as an anti-angiogenesis agent. In order to determine this possibility, consequences of DS-4152 infusion on HIV-1 p24serum levels and CD4+cell counts over time are being examined in ongoing clinical trials in the United States on patients with AIDS-associated KS.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo study the diagnostic sensitivity and specificity of polymerase chain reaction (PCR) for the non-invasive diagnosis of progressive multifocal leukoencephalopathy (PML) in HIV-1-infected individuals.DesignRetrospective analysis of stored cerebrospinal fluid (CSF) samples by PCR of HIV-1-infected patients.MethodsResults of the PCR analysis of the CSF of three AIDS patients with autopsy-proven PML were compared with the results in 15 neurologically asymptomatic HIV-1-infected patients and with 15 AIDS patients with other opportunistic infections of the central nervous system (CNS). A polyclonal antiserum to simian virus 40 (SV40) cross-reacting with JC virus (JCV) late antigens was used for immunocytochemical confirmation of the diagnosis. Two different primer pairs, one taken from the VP1/large T gene and the other from the large T gene, were used to amplify JCV-specific DNA sequences from CSF.ResultsFive CSF samples were analysed and JCV-specific DNA found in three patients with autopsy-proven PML. No JCV-specific DNA was detected in 47 CSF samples, including serial samples from 14 of the 30 non-PML patients. The diagnosis of PML was confirmed in all three cases by immunocytochemistry.Conclusion:PML can be diagnosed by PCR analysis of CSF. The sensitivity and specificity of the method depends on the sensitivity of the primers used for amplification. Using a primer pair from the large T gene, JCV-specific DNA was amplified in three cases with PML as early as the day of presentation with the first neurological symptom of PML.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveA Phase I study of subcutaneous recombinant interleukin-2 (rlL-2).DesignSixteen patients with advanced HIV infection receiving 600–1200mg zidovudine per day were divided into three groups, which received sequentially 0.2 x106, 0.7x106or 2x106units/m2per day of rlL-2 subcutaneously for 5 consecutive days.SettingFive-day admission to an academic tertiary care hospital.Patients, participantsSixteen unblinded, non-randomized volunteers.InterventionsSubcutaneous rlL-2.Main outcome measuresTolerance, toxicity, hematologic, immunologic and antiviral responses.ResultsrlL-2 was well-tolerated at the highest dosage, except in two patients who developed significant lymphopenia by the second day of rlL-2 administration, with rebound within 48 h after rlL-2 therapy. The number of eosinophils, CD4+ and CD8+ cells, and percentage of CD16+ (natural killer) cells, remained elevated above baseline for up to 10 weeks. Circulating rlL-2 receptor levels increased transiently during and immediately following rlL-2 administration. A twofold increase in natural killer cell activity against uninfected and HIV-infected targets was observed, but did not persist beyond 10 weeks following rlL-2 administration. There was a transient decrease in blastogenesis to phytohemagglutinin of patients receiving the highest dose of r-IL-2, but no significant change in viral burden.ConclusionsSubcutaneous rlL-2 in advanced HIV-infected patients on zidovudine was tolerated with side-effects similar to intravenous IL-2.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundIncreasing evidence suggests significant involvement of the basal ganglia in patients with HIV-1 infection.ObjectiveTo study the effect of HIV-1 infection on cerebrospinal fluid (CSF) dopamine levels.DesignCSF dopamine levels were measured by high-performance liquid chromatography.SettingA university-based outpatient clinic in south Florida involved in clinical AIDS research.SubjectsTwenty-two subjects were enrolled in a prospective, longitudinal study of the neurological complications of AIDS. Five subjects were HIV-seronegative, but at risk for HIV-1 infection, 11 were HIV-1-seropositive without neurological disease and six had HIV-1-related neurological disease.ResultsThe CSF dopamine mean values were significantly lower in the HIV-1-seropositive group with (P< 0.0001) or without (P< 0.0001) neurological disease than in the HIV-seronegative group. There was a very strong correlation between CD4 lymphocyte counts and CSF dopamine levels (P=0.004) in the neurologically symptomatic group (P= 0.0008), but not in the other two groups.ConclusionHIV-1 infection appears to have an effect on the central nervous system dopaminergic systems, as reflected in levels of CSF dopamine.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectivesWe evaluated time from HIV seroconversion to diagnosis of two common oral lesions associated with HIV infection and disease progression.DesignOral examinations were performed on homosexual and bisexual men enrolled in prospective cohorts.SettingHomosexual and bisexual men were followed in three epidemiologic cohort studies in San Francisco, California, USA.ParticipantsData were evaluated from 80 men with well-defined dates of HIV seroconversion from 1984 through 1991.Main outcome measuresWe determined the cumulative incidence of oral candidiasis and hairy leukoplakia after HIV seroconversion.ResultsFour per cent of men developed oral candidiasis within 1 year after HIV seroconversion, 8% within 2, 15% within 3, 18% within 4, and 26% within 5 years. Nine per cent developed hairy leukoplakia within 1 year, 16% within 2, 25% within 3, 35% within 4, and 42% within 5 years. The median CD4+ count was 391 x106/l when oral candidiasis was first reported and 468x106/l when hairy leukoplakia was first reported.ConclusionsOral candidiasis or hairy leukoplakia appeared in a significant proportion of HIV-infected homosexual and bisexual men. These lesions occurred relatively soon after HIV seroconversion, typically before AIDS. Evaluation of HIV-infected individuals for these lesions has many potential clinical and research benefits, including the possible use of oral lesions as primary end-points in clinical trials.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID