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1.
OBJECTIVES: To antagonize the deleterious effects of the HIV-1 toxin extracellular Tat on uninfected immune cells, we developed a new strategy of anti-HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid has been assayed for safety and immunogenicity in seropositive patients. METHOD: The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa 51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although biologically immunocompromised individuals (500-200 CD4+ cells/mm3). RESULTS: Following as many as 8 injections, no clinical defects were observed. All patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in vitro. CONCLUSION: These results provide initial evidence of safety and potency of Tat toxoid vaccination in HIV-1-infected individuals.  相似文献   

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We have observed a treatment-associated autoproliferative response in cultured peripheral blood mononuclear cells (PBMC) of asymptomatic HIV-1-infected subjects receiving a gp120-depleted, inactivated HIV-1 antigen in incomplete Freund's adjuvant (IFA; HIV-1 Immunogen). The frequency and magnitude of the autoproliferative response appeared to be dose-related (P < 0.05), and was not observed in subjects receiving IFA alone. Immunophenotyping of the proliferating cells demonstrated the presence of both CD4+ and CD8+ lymphocytes, with the CD4+ blasts almost exclusively expressing the CD45RO+ phenotype. A comparison of this response with the HIV-1-specific antigen stimulation responses in this cohort revealed a significant correlation between increases in HIV-1-specific cell-mediated immunity and autoproliferation (r2 = 0.61, P < 0.001). These findings suggest that immunization with the HIV-1 Immunogen induces an autoproliferative response that may reflect changes in HIV-1-specific cell-mediated immunity in infected individuals.  相似文献   

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BACKGROUND: Estimates of the prevalence of colonization with methicillin-resistant Staphylococcus aureus (MRSA) vary in HIV-infected patients. METHODS: HIV clinic patients were prospectively cultured. Bilateral nasal and axillary swabs were plated on BBL CHROMagar MRSA media. Molecular typing was done by pulse-field gel electrophoresis, and staphylococcal cassette chromosomemec typing was determined. A patient questionnaire was conducted to ascertain potential MRSA risk factors; medical records were reviewed. RESULTS: Fifteen of 146 (10.3%) patients had MRSA nasal colonization; 1 also had axillary colonization. Twelve of 15 isolates were staphylococcal cassette chromosomemec type IV, and 8 of 14 were USA300 or USA400 genotype. MRSA colonization was associated with lower CD4 cell count, not receiving current or recent antibiotics, history of prior MRSA or methicillin-susceptible Staphylococcus aureus infection (P < 0.05 for all), and a trend toward history of hospitalization or emergency department visit in the past year (P = 0.064). Current use of trimethoprim-sulfamethoxazole was protective for colonization: 0 of 29 trimethoprim-sulfamethoxazole recipients were colonized versus 15 of 117 nonrecipients, P = 0.04. In a multivariate logistic regression model, prior infection with either methicillin-susceptible S. aureus (odds ratio = 32.4, 95% confidence interval 3.04 to 345.42) or MRSA (odds ratio = 9.71, 95% confidence interval 2.20 to 43.01), not receiving current or recent antibiotics (odds ratio = 0.026, 95% confidence interval 0.002 to 0.412), and lower CD4 count (odds ratio 0.996, 95% confidence interval 0.992 to 0.999) were associated with MRSA colonization. DISCUSSION: The prevalence of MRSA nasal colonization was relatively high compared with prior studies; axillary colonization was rare. Prior staphylococcal infection (methicillin-susceptible S. aureus or MRSA), not receiving antibiotics, and lower CD4 count were associated with MRSA nasal colonization. Trimethoprim-sulfamethoxazole seemed to be protective of MRSA colonization.  相似文献   

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Memory B cells are long-living cells that circulate throughout the body and differentiate into plasma cells after stimulation by antigens, cytokines, and direct cell-to-cell interaction in lymphoid tissues. For HIV-1-infected patients, we assessed whether in vitro polyclonal B cell activation that induces immunoglobulin secreting cells (SCs) also generates HIV-1-specific resting B cells to synthesize antibodies specific to HIV-1. To this end, highly purified B cells from 10 HIV-1-untreated patients were cultured with or without mouse fibroblastic cells expressing the CD40 ligand in the presence of IL-2 and IL-10. The percentage of immunoglobulin SCs we obtained by using the B cell-CD40L stimulation system was equal to 55% to 98% of the circulating memory B cells. Moreover, the anti-HIV-1 IgG, IgA, or IgM antibody SCs represented 1 x 10-2 to 1 x 10-3 of the total immunoglobulin SCs. The anti-HIV-1-specific antibodies detected in cell culture supernatants were directed to gag-, pol-, and env-encoded viral proteins. We found that in AIDS patients, HIV-1-specific resting memory B cells circulate in the blood and can be quantified by their anti-HIV-1 antibody secretion after strong B cell polyclonal stimulation.  相似文献   

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We tested the hypothesis that the loss of immunological reactivity in HIV-1-infected persons may result partly from a virus-induced metabolic disorder. Patients who are infected with the acquired immunodeficiency syndrome (AIDS)-associated human immunodeficiency virus 1 were found to have, on average, markedly elevated and highly variable plasma glutamate concentrations. A similar elevation of the extracellular glutamate concentration was found to inhibit DNA synthesis in cultures of mitogenically stimulated lymphocytes. An even stronger inhibition was seen with the structural analogue quisqualate, and a moderate inhibition was seen with N-methyl-D-aspartate and kainate, i.e. with well established pharmacological probes for the excitatory glutamate receptors in the vertebrate central nervous system. The inhibitory effect of glutamate was compensated by adding cysteine or relatively large numbers of 'splenic adherent cells' to the culture. Elevated extracellular glutamate levels were also found to reduce the capacity of murine macrophages, human blood monocytes, and murine fibroblastoid cells (L929 cells) to release acid-soluble thiol (cysteine) into the extracellular space. The three cell types differed, however, with respect to their sensitivity against the three structural analogues of glutamate. The elevated glutamate concentration was not non-specifically toxic for cultured macrophages, since glycolytic activity and arginase activity were not inhibited. Implications of these observations for the pathogenetic mechanism of AIDS are discussed.  相似文献   

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The prevalence of antibody to hepatitis C virus (HCV) in a cohort of 272 HIV-infected patients was assessed by means of 4 anti-HCV assays: a 1st generation and a neutralization test, a 2nd generation test, and a confirmatory test, the dot-blot Matrix HCV? immunoassay. The cohort included, as a single risk factor, 35.7% intravenous drug users (IVDUs), 25% homosexual men, 30.1% heterosexual individuals, 5.9% transfused patients, 0.7% occupational infections, and 2.6% patients with unknown infection source, and was studied on entry and in samples collected for up to 36 months. Results showed that on entry (i) sera of 83 out of 272 members of the cohort were positive by the HCV 1st generation EIA (30.5%); 70 were confirmed by the neutralization test (84.3%); (ii) 115 of the cohort were reactive with the 2nd generation HCV EIA (41.3%); (iii) with the dot-blot immunoassay 99 (86.1%) of the cohort were confirmed and 16 remained indeterminate. The overall confirmed HCV antibody-positive rate in these 272 patients was 36.4%. Antibody to HCV was detected in 78.3% of IVDUs, 18.3% of heterosexual individuals, 31.2% of transfused patients, and only 2.9% of homosexual men. The 36-month follow-up of this cohort revealed that 4/145 patients became anti-HCV positive by second generation assay. Hepatitis B markers were frequently associated with HCV in IVDUs (71.1%) but infrequently in heterosexual (8.5%) or homosexual (1.5%) individuals. Our results suggest that HCV 2nd generation EIA used in combination with the semiautomated dot-blot assay as a confirmatory test improves the specificity and sensitivity for HCV antibody detection. Homosexual males are at low risk of HCV infection among HIV risk groups. © 1994 Wiiey-Liss, Inc.  相似文献   

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The beta-chemokines, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, monocyte chemotactic protein (MCP)-1 and regulated-on-activation normal T cell, expressed and secreted (RANTES) are not only chemotactic for mononuclear cells but may be important in suppression of HIV-1 replication through competitive binding to the chemokine receptor, CCR5, which is critical to viral entry. In this study, bronchoalveolar cells (BACs) and autologous peripheral blood mononuclear cells (PBMCs) were obtained from HIV-1-infected participants who did not manifest clinical signs of lung disease with peripheral CD4 T-cell count >200/mm(3) (n = 7, group with high CD4 count), or CD4 T-cell count <200/mm(3) (n = 12, group with low CD4 count), and from healthy study subjects (n = 5). The capacity to express beta-chemokines and CCR5 was assessed. Induction of MIP-1 alpha by lipopolysaccharide (LPS) in BAC of HIV-1-infected study subjects from the low CD4 group was less than BAC from healthy study subjects (p <.001), and also was less than in BACs from the group with a high CD4 group (p <.001). Moreover, the intracellular expression of MIP-1 alpha in LPS-induced monocytes of HIV-1-infected patients was significantly less than that from healthy study subjects (p <.01). In addition, spontaneous expression of mRNAs for CCR5 and MIP-1 alpha in BAC was significantly lower in HIV-1-infected patients compared with in healthy study subjects (p <.03 and p <.02, respectively). In contrast to the findings with MIP-1 alpha, LPS stimulated MCP-1 in BAC from the group of HIV-1-infected patients with high CD4 count was significantly higher than healthy study subjects (p <.001). These dysregulations in the ability to express beta-chemokines by BAC may be important in the progression of HIV-1 infection in the lung.  相似文献   

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BackgroundEnfuvirtide (ENF) is a viral fusion inhibitor used in patients failing highly active antiretroviral therapy (HAART). Mutations associated with ENF resistance have been identified within amino acid positions 36–45 of gp41. As ENF will be introduced to Hong Kong, an understanding of the prevalence of naturally occurred ENF resistance mutations is important before implementation of ENF treatment.ObjectivesTo investigate the prevalence of ENF resistance-associated mutations in the HR1 and HR2 of HIV-1 strains obtained from ENF-naïve patients.Study designHIV-1 strains isolated from 185 patients (156 antiretroviral treatment [ART]-naïve and 29 HAART-experienced) were screened for ENF resistance-associated mutations using RT-PCR and DNA sequencing.ResultsPrimary mutations were detected in 19.4% of HARRT-experienced patients and 20.5% of ART-naïve patients. G36D was encountered most frequently and more prevalent in non-B subtypes. N42S, L54 M and V69I were the major polymorphisms detected. N42S and L54M were predominant in CRF01_AE and subtype B, respectively. V69I was found in all samples harboring G36D. In three longitudinal samples from an ENF-treated patient, G36D was detected after ENF treatment for 6 months and the mutation persisted after termination of ENF for 6 months.ConclusionsThe high prevalence of ENF resistance-associated mutations in HARRT-experienced and ART-naïve patients identified in this study highlights the importance of mutation screening before ENF therapy in Hong Kong. Our findings from the ENF-treated patient showed that G36D mutation persisted as long as 6 months after ENF withdrawal. Phenotypic assays will be necessary to confirm the influence of this mutation to ENF susceptibility.  相似文献   

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The way in which the extensive use of highly active antiretroviral therapy (HAART) has influenced the incidence of visceral leishmaniasis (VL) among human immunodeficiency type 1 (HIV-1)-infected patients is not yet understood. The present study assessed whether the incidence of symptomatic VL in HIV-infected patients has decreased since the introduction of HAART. Likewise, the role of other potential risk factors for VL was also analyzed. Therefore, 479 HIV-1-infected patients receiving antiretroviral treatment, according to the available drugs at each moment, were prospectively followed from April 1989 to June 2000 in two university hospitals in southern Spain. A bone marrow aspiration was performed when patients showed symptoms suggestive of kala-azar. A diagnosis of VL was made when Leishmania amastigotes were seen in Giemsa-stained samples or promastigotes were cultured in specific media. The median follow-up time was 1,380 [8 to 4,536] days. Twenty-one patients were diagnosed with symptomatic VL. The density of incidence of VL has decreased 64.8% as of January 1997, when HAART began to be used extensively in our area. The use of HAART was the main independent factor associated with VL; this therapy was a protective factor (adjusted hazard ratio [HR], 0.05; 95% confidence interval [CI], 0.02 to 0.15). CDC clinical category C at entry in the cohort (HR, 4.08; 95% CI, 1.46 to 11.35) and CD4(+) cell counts below 300 cells/mm(3) during the follow-up (HR, 3.96; 95% CI, 1.56 to 10.01) were also independently associated with kala-azar. A VL diagnosis prior to follow-up and low compliance with antiretroviral therapy were not independently associated with symptomatic VL, although statistical significance was almost reached (P = 0.1 and P = 0.08, respectively). In summary, the use of HAART has led to a fall in the incidence of symptomatic VL in HIV-infected patients. The main risk factor associated with kala-azar emergence in patients infected with HIV is deep immunosuppression.  相似文献   

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Influenza vaccine is recommended for HIV-1-infected patients. The present prospective study was conducted to evaluate the clinical efficacy and immunologic responses to the vaccine. From November 1 to December 27, 2002, 262 HIV-1-infected patients received a trivalent influenza subunit vaccine, whereas 66 did not. Influenza illness occurred in 16 vaccinated and 14 nonvaccinated patients (incidence = 6.1% [95% confidence interval (CI): 4%-10%] in vaccinated vs. 21.2% [CI: 13%-35%] in nonvaccinated persons, P < 0.001; relative risk = 0.29 [CI: 0.14-0.55]). Influenza vaccine provided clinically effective protection against influenza illness in HIV-1-infected patients. In baseline antibody-negative patients, anti-H1 and anti-H3 antibody responses to the vaccination were significant in those patients with a CD4 count >200 cells/muL compared with those with a CD4 count <200 cells/muL (P < 0.05). In contrast, in baseline antibody-positive patients, good antibody responses were observed irrespective of CD4 counts, like the healthy controls. Based on these results, annual vaccination is recommended. Specific CD4 responses correlated with HIV-1 viral load (VL), especially in patients treated with highly active antiretroviral therapy (HAART) compared with those without HAART (P < 0.01), although the clinical efficacy did not correlate with HIV-1 VL. HAART may enhance the immunologic efficacy of influenza vaccine.  相似文献   

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Prevalence and predictors of transmitted drug resistance (TDR), defined as the presence of at least one WHO surveillance drug resistance mutation (SDRM), were investigated in antiretroviralna?ve HIV-1-infected patients, with a genotypic resistance test (GRT) performed ≤6 months before starting cART between 2000 and 2010. 3163 HIV-1 sequences were selected (69% subtype B). Overall, the prevalence of TDR was 12% (13.2% subtype B, 9% non-B). TDR significantly declined overall and for the single drug classes. Older age independently predicted increased odds of TDR, whereas a more recent GRT, a higher HIV-RNA and C vs. B subtype predicted lower odds of TDR.  相似文献   

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Rahim S  Ortiz O  Maslow M  Holzman R 《The AIDS reader》2004,14(1):23-4, 29-32, 35-40
Gynecomastia has been reported to occur in HIV-infected patients receiving HAART. A retrospective case-control study was conducted to determine risk factors associated with this condition. Two control patients were randomly chosen for each of 23 case patients identified. An efavirenz-containing regimen was strongly associated with the development of gynecomastia (odds ratio, 20; P < .001). Case patients were not more likely to have lipodystrophy, low testosterone levels, chronic infection with hepatitis B or C virus, or liver dysfunction compared with control patients. None of these factors altered the efavirenz-associated risk when analyzed by multiple logistic regression. Efavirenz appears to be strongly associated with gynecomastia in HIV-infected patients receiving HAART.  相似文献   

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