ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To identify and characterize individuals with long-term HIV-1 infection who have experienced little or no progressive CD4+ T-cell loss during follow-up.Patients and methods:The rate of CD4+ T-cell loss (CD4 slope) was determined for each of the 290 participants in the San Francisco Men's Health Study who were seropositive at study entry in 1984. The study population was stratified, by CD4 slope, into 10 groups of 29 individuals and each group was characterized using a variety of cross-sectional and longitudinal laboratory measurements.Results:Approximately 10% of the HIV-1-infected men experienced no net CD4 + T-cell loss during 78 months of follow-up. Compared with all other seropositive subjects, these ‘non-progressors' were the extreme cases in a relatively continuous distribution of CD4 slopes, rather than a discrete subpopulation. Although they had no net cell loss, their mean CD4+ cell count was approximately 400 × 106/l lower and their mean CD8+ cell count approximately 250 × 106/l higher than seronegative subjects, suggesting early changes followed by stabilization. The CD4 slope was associated with the levels of β2-microglobulin, neopterin, p24 antibody, erythrocyte sedimentation rate, viral burden, and the proportion of HIV-1 isolates with tropism for the MT-2 T-cell line. Multivariate cluster analysis of these laboratory markers did not distinguish the non-progressors as a distinct subgroup.Conclusions:These findings support both a biphasic natural history and the suggestion that the broad range in HIV disease progression rates may be the result of several independent factors interacting in a variety of combinations. Recent changes in laboratory markers, known to predict both CD4+ cell loss and AIDS, suggest that non-progressors are undergoing slow HIV disease progression.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To investigate the relationship between cytokine serum levels, peripheral blood lymphocyte subsets and clinical picture in acute primary HIV-1 infection.Patients and methods:Absolute number/μl total lymphocytes, CD4+, CD8+ and natural killer (NK) cells, as well as serum levels of soluble CD8 receptor, interleukin (IL)-1β, IL-2, lL-4, IL-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, β2-microglobulin and 5′-neopterin were determined in 15 patients with acute primary HIV-1 infection, 16 asymptomatic HIV-1-seropositive individuals and 18 HIV-1-seronegative individuals at risk for HIV-1 infection.Results:Acute primary HIV-1 infection was characterized by significant CD4+ lymphocytopenia with low IL-2 serum concentrations, and by high absolute number of circulating CD8+ and NK cells, with elevated serum levels of soluble CD8 receptor, IL-1β, IFN-γ and 5′-neopterin. Follow-up of acute seroconverters showed a significant decrease in NK cell counts and 1L-1β levels, with an increase of IL-6.Conclusions:In acute primary HIV-1 infection, significant alteration of cytokine release, possibly induced by viral antigens, could be responsible for both clinical picture and activation of cytotoxic cells through abnormal mechanisms.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:In this 2.5-year study of simian immunodeficiency virus (SIVsm) infection in rhesus monkeys, quinolinic acid (QUIN) levels and virus isolation determinations were made in serial cerebrospinal fluid (CSF) and blood samples to evaluate the relationship between these parameters over the course of infection.Methods:Eight rhesus monkeys were inoculated in the saphenous vein with SIVsm. Four animals were maintained as uninoculated controls. CSF and blood samples were obtained every 1–4 weeks over the course of study. SIV isolation was determined in H9 cells for the CSF and in primary rhesus lymphocyte co-cultures for peripheral blood mononuclear cells (PBMC). QUIN was quantitated in CSF and serum by electron-capture negative chemical ionization gas chromatography mass spectrometry.Results:All SIV-inoculated animals became CSF and PBMC isolation-positive by 1–3 weeks post-inoculation. Control animals remained SIV-negative. One SIV-positive animal was humanely euthanized at 2 weeks post-inoculation. The three SIV-inoculated animals that were CSF isolation-negative after the fifth week post-inoculation maintained CSF QUIN values <100nM, remained CSF and PBMC isolation-negative, and clinically healthy in the chronic course of disease. In contrast, the four SIV-inoculated animals that were CSF isolation-positive 6–8 weeks post-inoculation had CSF QUIN levels as high as 153–565 nM during the second month post-inoculation and remained CSF virus isolation-negative, persistently PBMC isolation-positive, and experienced clinical symptoms of SIV in the chronic course of disease. Three of these four animals have succumbed to SIV infection.Discussion:Initial QUIN responses and viral isolation status in the first month post-inoculation were consistent among SIV-inoculated animals with CSF and serum QUIN values significantly higher than those of controls. A divergence within the SIV-inoculated group of animals became apparent within the second month of primary SIV infection and was maintained throughout the course of infection. Persistent PBMC viral isolation and marked elevations of QUIN were linked to symptomatic disease and a poor prognosis for survival. Predominantly negative PBMC viral isolation and slight, but significant, elevations of QUIN were linked to asymptomatic disease with a favorable prognosis for survival.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To determine whether synergistic inhibition of HIV-1 replication would result from thein vitrouse of nevirapine in combination with zidovudine, interferon (IFN)-α 2C, and CD4 immunoadhesin.Design and methods:The non-nucleoside reverse transcriptase inhibitor nevirapine (formerly BI-RG-587) was tested in combination with the other antiretroviral agents. Assays were performed on stimulated peripheral blood lymphocytes infected with HIV-1. Virus replication was assessed by the release of viral p24 antigen into culture supernatants. The median-effect principle was used to assess for synergistic interactions of the combined agents.Results:Zidovudine, IFN-α 2C and CD4 immunoadhesin, when used in combination with nevirapine, synergistically inhibited HIV-1 replication in human peripheral blood lymphocytes compared with each agent used alone. Some analyses were also consistent with additive effects, but antagonism was not noted.Conclusion:Thesein vitrofindings provide a scientific basis for future trials with similar drug combinations.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To evaluate the frequency of dual HIV-1 and HIV-2 DNA sequences in patients with dual serological profiles.Design:We tested 40 samples from AIDS patients living in Abidjan, Côte d'lvoire.Methods:Dual serological reactivity was determined by double Western blot and two enzyme-linked immunosorbent assays with recombinant proteins and synthetic peptides as antigens. The Western blot was considered to show dual reactivity when sera reacted with at least two glycoproteins and one core protein of each virus. HIV DNA sequences were detected by hybridization to radiolabelled probes of polymerase chain reaction (PCR) products amplified using specific primers.Results:Both HIV-1 and HIV-2 DNA sequences were detected in four out of 11 samples with a dual serological profile and in four out of 24 samples with anti-HIV-1 antibodies only.Conclusion:These results show that dual HIV-1 and HIV-2 serological profiles are not always due to infection by both viruses, and emphasize the need for a combination of serological and PCR assays for the appraisal of these viral infections.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To examine the genetic heterogeneity of the V3 region of HIV-1 gp120 from 22 Brazilian HIV-1 specimens.Design:Genetic heterogeneity was examined by DNA sequencing of the C2 V3 region of the HIV-1 envelope (env) gene from polymerase chain reaction (PCR)-amplified HIV-1 DNA. Deduced amino-acid sequences were compared to determine the extent of amino-acid conservation among the Brazilian specimens. Genetic similarity among and between the Brazilian specimens and other previously published HIV-1 isolates was analyzed by principal co-ordinate and DNA parsimony methods.Methods:A 282 base pair (bp) region of a 1.5 kilo (k) bp PCR-amplified HIV-1 env fragment was sequenced by aTaqdye-labeled primer cycle sequencing reaction. Nucleotide sequences were used to analyze inter-specimen relationships based on overall nucleotide sequence similarity and DNA parsimony principles.Results:Amino-acid comparison showed that 15 of the 35 (43%) residues of the V3 loop were conserved among the Brazilian specimens. Nine of the 22 (40%) Brazilian specimens contained the North American—European GPGR tetrapeptide motif, while eight (36%) contained the GWGR motif, previously reported in Japanese isolates. Principal co-ordinate analysis demonstrated that 19 of the 20 examined Brazilian HIV-1 specimens were more similar to North American and Haitian isolates than to African isolates. Similar results were also obtained by DNA parsimony analysis.Conclusion:The majority of the Brazilian specimens examined are more genetically related to North American and Haitian HIV-1 isolates than to African isolates. This finding and the presence of a GWGR V3 loop motif in some Brazilian isolates may be important for vaccine development.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To carry out, within France, a large-scale molecular epidemiological investigation on the principal neutralizing determinant of HIV-1, located in the third variable region (V3) of the envelope protein. Such investigations are of the utmost importance in the identification and monitoring of the distribution and spread of different viral strains internationally.Design:Using polymerase chain reaction (PCR), we examined the genetic variation of the V3 region sequences of 28 HIV-infected patients from Paris, France.Results:Comparison of the Parisian V3 loop sequences with other published data indicates that the range of diversity in France is included within that of a large group that contains sequences from North America, the rest of Europe, Japan, India and Africa. Variability appears to be lower in the V3 loop than in its flanking regions. Five out of the six putative N-linked glycosylation sites show preferential alterations to charged amino acids. We report two motifs at the tip of the loop that have not been described previously.Conclusions:The structural homogeneity and the wide geographic representation of the major V3 group suggests that a common strategy could be applied to a large proportion of isolates in the development of a broad-spectrum HIV vaccine.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:Since the chlorite—oxygen reaction product tetrachlorodecaoxygen (TCDO) anion complex promotes efficaciously tissue repair and has antibacterial activity, our aim was to determine the effects of TCDO on the replication of HIV and on the infectivity of free HIV particles.Design:The effects of TCDO on cellular HIV replication machinery and the consequences of TCDO for infectivity of HIV virions were evaluated.Methods:Virus yields in supernatants of TCDO-supplemented cultures of HIV-infected cells or virus infectivity in TCDO-treated virus stocks were quantified by titration assays and then calculating the 50% tissue culture infectious dose.Results:First, TCDO did not affect the replication of HIV in persistently infected lymphocytic and monocytic cell lines or in peripheral blood mononuclear cells. Second, supplementation of HIV stocks with TCDO markedly decreased the infectivity of HIV particles in a concentration dependent manner. Third, the binding of gp120 envelope glycoprotein of HIV-1 to cells is blocked by pre-incubation with TCDO. Fourth, the inhibition of HIV replication by the reverse transcriptase inhibitor 3′-azido-3′-deoxythymidine (zidovudine) inde novoinfected cell cultures was not affected by the simultaneous addition of TCDO. However, the delayed virus spread of HIV in cultures in the presence of suboptimal concentrations of zidovudine could significantly be blocked by the simultaneous addition of TCDO. Fifth, TCDO failed to induce the chromosomally integrated HIV-1 provirus in the T-lymphoma cell line ACH2.Conclusions:TCDO appears to inactivate HIV particles directly, but has no influence on the intracellular replicative machinery of HIV. Our results suggest that a clinical evaluation of the TCDO complex as chemotherapy for HIV infection and full-blown AIDS should be considered, particularly in patients concomitantly receiving zidovudine.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To estimate the influence of fever, diarrhoea, stage of HIV disease, opportunistic infection and anorexia on malnutrition in HIV-infected patients we analysed data of patients undergoing a nutritional counselling programme from November 1989 to April 1992.Patients and methods:Our study group comprised 104 HIV-infected patients (98 homosexual men, 15 asymptomatics, 30 AIDS-related complex patients, 59 AIDS patients). Nutritional status was measured by previous weight loss, bioelectrical impedance analysis and prospective intake protocol.Results:Patients had lost 10 ± 8.7% of body weight. Compared with controls, body mass index was lower (P< 0.001), and extracellular/body cell mass ratio (ECM/BCM) was higher (P< 0.001). BCM was reduced proportionately to weight loss, percentage of body fat was lower compared with controls (P< 0.001), even in patients with stable weight. Clinical risk factors for malnutrition were identified as fever in 31, diarrhoea in 26, acute infections in 42 and anorexia in 73 out of 104 patients. One single risk factor was predominant in 63 patients: fever in five, diarrhoea in 14, acute infections in 17 and anorexia in 27 patients. Weight loss was not linearly correlated to CD4 count or to time since AIDS diagnosis. Food intake was highly variable (39–165% of calculated needs) without correlation to weight loss.Conclusions:Loss of body fat was found even in the earlier stages of HIV infection and was more severe than loss of BCM. Important risk factors for malnutrition are anorexia (most frequent), diarrhoea and fever (most severe). Most patients have combined risk factors. Treatment strategies and pathophysiologic studies should consider the heterogeneity of HIV-associated malnutrition.

ISSN:0269-9370    

出版商:OVID    

年代:1993

数据来源: OVID