摘要:

Summary:Staphylococcus aureushas been recognized as a common cause of bacteremia of such infections in human immunodeficiency virus type 1 (HIV-1) seropositive patients. Some staphylococcal exotoxins are recognized as superantigens. We have found that superantigen toxic shock syndrome toxin-1 (TSST-1) brings about a high level of viral production in HIV-1-infected peripheral blood mononuclear cells (PBMCs) through their activationin vitro. The p24 antigen level in the culture supernatant markedly increased in the presence of TSST-1 at a concentration of 1 pg/ml or higher. Fluorescent-activated cell sorter analysis revealed that TSST-1 specifically activated CD4+T lymphocytes. Although significant production of tumor necrosis factor α (TNF-α) was observed in uninfected PBMCs treated with TSST-1 after 96 h of incubation, much earlier (after 12 h of incubation) production of TNF-α was identified in HIV-1 infected PBMCs with or without TSST-1 treatment. The addition of anti-TNF-α antibody to the culture medium resulted in a dramatic decrease in HIV-1 replication. These results suggest that the enhanced replication of HIV-1 by TSST-1 in PBMCs is attributable mainly to the activation of CD4+T lymphocytes and that the induction of TNF-α further enhances replication. Since the enhancement of HIV-1 replication by TSST-1 occurs in a concentration range of picograms per milliliter, the superantigen TSST-1 may play an important role in the pathogenesis and clinical course of HIV-1 infections.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:Ten asymptomatic individuals who had experienced only limited CD4+cell loss after prolonged infection with HIV-1 were studied. These individuals had a mean CD4+cell count of 674 × 106cells/L and a mean duration of infection of 8.5 years. Also included were 10 asymptomatic HIV-1-infected individuals who, over a similar period of infection (7.5 years), had experienced a profound loss of CD4+cells (mean CD4+cell count, 54 × 106cells/L). Proviral load was determined using a semiquantitative polymerase chain reaction and was significantly lower in the subjects with slowly progressing infection (SPI) than in subjects with rapidly progressing infection (RPI) (4,000 vs. 40,000 proviral copies/106peripheral blood mononuclear cells;p= 0.0089). Isolation of virus was attempted in all individuals but succeeded only in 6 of 10 individuals with SPI versus all 10 individuals with RPI. Four of six virus isolates obtained from individuals with SPI and 6 of 10 obtained from individuals with RPI were of the syncytia-inducing phenotype. We determined the neutralizing activity of serum against HIVMN, HIVIIIB, and the contemporaneous autologous isolate when available. Serum from individuals with SPI generally neutralized the contemporaneous isolate, whereas serum from individuals with RPI did not [geometric mean antibody titer (GMT), 45 vs. 3;p= 0.0047]. There was no difference in neutralizing ability against HIVMN(GMT,2,593 vs. 2,263;p= 0.74) and only a small difference against HIVIIIB(GMT, 115 vs. 50;p= 0.075). Our results indicate that individuals with SPI are characterized by an ability to neutralize their own HIV strain. In contrast, neutralizing activity against HIVMNand HIVIIIBdid not distinguish individuals with SPI from individuals with RPI.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:In HIV-1–infected cell cultures, a relatively low concentration (5 μg/ml) of monoclonal antibody (mAb) against HIV-1–transactivating Tat protein was an efficient inhibitor of HIV-1 replication both in HIV-1(IIIB)–infected Jurkat cell and peripheral blood mononuclear cell (PBMC) cultures and significantly reduced the expression of a Tat-responsive CAT-reporter construct in HIV-1(IIIB)–infected Jurkat cells. Anti-Tat mAb also caused a significant reduction and a consistent delay in HIV-1 replication when added to PBMCs from HIV-1–infected patients cocultivated with phytohemagglutinin (PHA)-stimulated normal PBMCs. These data indicate that an autocrine–paracrine loop sustained by extracellular Tat protein, which is actively released by HIV-1–infected cells, may affect HIV-1 replication in cell cultures in vitro. An inverse relationship between natural anti-Tat antibody levels and p24 antigenemia was demonstrated by retrospective analysis of serial serum samples obtained from 10 HIV-1–seropositive hemophiliac patients followed over a 7–9-year period. This datum points to a possible influence of anti-Tat antibody on the progression of HIV-1 disease in vivo. These findings have strong implications for Tat protein as a possible target for specific immunotherapy in HIV-1–infected patients.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:HIV-specific cytotoxic T lymphocytes (CTLs) are an important component of the host immune response against HIV infection, and these cells release a variety of cytokines when they meet their target antigen. Since the phosphodiesterase inhibitor pentoxifylline is being used as a therapeutic agent in clinical trials of HIV infection due to its inhibitory effect on virus replication in vitro, we examined the effect of pentoxifylline on cytotoxicity and cytokine secretion by HIV-specific CD8+CTLs. Pentoxifylline inhibited cytotoxicity of CTLs and suppressed interferon-γ, tumor necrosis factor–α, and granulocyte–macrophage colony-stimulating factor release by these cells at the transcription level. Suppression of cytokine release resulted in reduced capacity of the CTLs to induce HLA class I and ICAM-1 expression and to stimulate HIV-1 replication. These results suggest that inhibition of HIV-specific CD8+CTLs by pentoxifylline may be therapeutically relevant. Moreover, this study extends previous observations by demonstrating that, in addition to its ability to suppress cytokine production by macrophages and CD4+T helper cells, pentoxifylline may inhibit cytotoxicity and cytokine secretion by antigen-specific CD8+cytotoxic T lymphocytes.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:We quantified HIV-1 RNA levels (copies per milliliter) in cerebrospinal fluid (CSF) and serum from subjects at various stages of HIV-1 disease and determined the relationship of RNA levels to clinical and neurologic disease status (HND) and to laboratory values. Ninety-seven HIV-1-seropositive men without CNS opportunistic infections, tumors, or neurosyphilis and 13 high-risk seronegative controls were included in the study. Each individual underwent a structured interview and physical and neurologic examinations, followed by standardized collection of blood and CSF. A custom-designed, fully automated polymerase chain reaction (PCR) system was used to perform a minimum of four separate amplifications per specimen, using two HIV-1gagprimer pairs. Southern blotting followed by hybridization with product-specific probes was used for post-PCR detection. The number of copies per milliliter was determined by relating unknowns to a built-in dilution-series standard curve using an image analysis system. HIV-1 RNA was detectable in 96% of the sera, 78% of the concentrated CSF samples, and 54% of the unconcentrated CSF samples. Serum RNA levels were significantly higher than in CSF. Serum RNA levels were significantly inversely correlated with CD4+cell counts (ρ = –0.34;p= 0.03): i.e., higher RNA levels in seropositive subjects were associated with lower numbers of CD4+cells. Serum RNA levels correlated positively with number of AIDS-related symptoms, dysfunction scores for total neurological examination, mental status score, cranial nerve score, and CNS motor signs score. Serum RNA levels did not correlate significantly with length of time on zidovudine therapy, intrathecal IgG synthesis rate, or albumin leakage. RNA levels in CSF significantly correlated only with intrathecal IgG synthesis rate and with serum RNA levels. These results confirm that serum levels of HIV-1 RNA correlate with HND and inversely correlate with CD4 counts, demonstrating that HND occurs predominantly in late stages of HIV-1 disease, although HIV-1 RNA can be detected in CSF from a majority of HIV-1–seropositive individuals at all stages of disease, which suggests that there can be early penetration of HIV into the CNS. However, HND can occur in the absence of high levels of CSF HIV-1 RNA. We also found that the concentration of HIV-1 in CSF is correlated with intrathecal IgG synthesis rate.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:A cohort of human immunodeficiency virus (HIV)-discordant couples was established to evaluate risk factors associated with heterosexual viral transmission. Polymerase chain reaction (PCR) was utilized to document the HIV-uninfected status among members of discordant heterosexual couples and to rule out immunosilent infection. HIV DNA PCR specific for agaggene region was performed on peripheral blood mononuclear cell samples from 203 HIV antibody-negative adults who have long-term heterosexual relationships with HIV-infected partners. The results were negative for 200 but consistently positive in three individuals. More extensive evaluation of these three individuals with an additional primer pair specific for the envelope gene, quantitative DNA PCR, multiple additional time points, and variable nucleotide tandem repeat analyses revealed specimen processing problems in two cases but an apparent true positive PCR assay in the third case. This subject remains antibody and PCR negative for a 32-month follow-up period. These results confirm previous studies that document a negligible incidence of occult HIV infection as delineated by PCR in antibody negative heterosexual partners of HIV-infected individuals. Specimen processing errors occur at a low rate (1% in this study) and require careful evaluation. The possibility of transient, aborted infection versus successful infection with a long immunosilent period was observed in a single individual. Definitive resolution of infection status will require long-term evaluation.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:We report three cases of zygomycosis (mucormycosis) occurring in three individuals infected with the human immunodeficiency virus (HIV) and review 12 other published cases. We present the only two case reports of disseminated zygomycosis in AIDS patients, and the only AIDS patient with renal zygomycosis to survive without nephrectomy, receiving intravenous (i.v.) amphotericin alone. Coinfection with zygomycosis and HIV is rare, occurs primarily in patients with low CD4+lymphocyte counts, does not always require the usual predisposing conditions for zygomycosis, and may be the presenting opportunistic infection among HIV-infected persons. Transient episodes of neutropenia occurring within 4 months before presentation may be a risk factor for this disease. Zygomycosis may arise in multiple sites including the basal ganglia, cutaneous tissue, kidney, respiratory tract, and may be disseminated. Occurring more commonly in, but not restricted to, injection drug users, it is significantly associated with sites other than basal ganglia in those patients with advanced HIV disease or AIDS. The presenting symptoms are related to the site of involvement, and the illness may develop insidiously or progress rapidly to a fulminant course. Successful therapy usually consists of surgical debridement and intravenous amphotericin B. Overall mortality in this review is 40%, and is significantly associated with sites of disease inaccessible to surgical debridement.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:We investigated the possibility that a secreted glycoprotein of ˜90,000 daltons, termed 90K and identified as a member of the protein super-family characterized by the scavenger receptor cysteine-rich (SRCR) domain, might have value as a predictor of progression to acquired immunodeficiency syndrome (AIDS) in subjects infected with the human immunodeficiency virus (HIV). Among 488 HIV-seropositive intravenous drug users with a median follow-up of 32.5 months, high levels of serum 90K at baseline proved to be a significant predictor of faster progression to AIDS, either as a continuous variable (log 90K;p< 0.0001) or as a dichotomous variable with an optimized cutoff point of 30 U/ml (p< 0.00001). Analysis of 90K in relation to known prognostic factors found an association with CD4 count, β2-microglobulin, and p24 antigen but none with neopterin. In multivariate analysis, the baseline 90K level was an independent predictor of AIDS. As compared with subjects with low levels of 90K, the relative risk of developing AIDS was 3.5 (95% CI 1.9–6.5) among those with high levels of 90K. The predictive value of 90K was maintained after stratification by baseline CD4 count: among subjects with ≥500 × 106/L CD4 cells, the proportion in whom AIDS developed was 10.5% for those with 90K levels ≤30 U/ml as compared with 20% for those with 90K above the cutoff point (p= 0.006). Serum 90K is an independent predictor of the risk for progression to AIDS in HIV-infected subjects, including those whose CD4 counts have not fallen.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:Studies from Kenya have reported rapid clinical disease progression among HIV-infected professional sex workers. The reasons for this rapid decline are unknown. To better understand factors influencing the course of disease, HIV-1 disease progression was explored in terms of declines in CD4 counts. Two samples from Nairobi, Kenya, were studied, one from a cohort of female sex workers and another, as a comparison group, from mothers enrolled in an HIV-1 vertical-transmission study. A Markov model was used to analyze transitions between HIV-1 disease stages as defined by CD4 counts. It appears that sex workers experience a rapid decline in CD4 counts, consistent with earlier findings of rapid clinical disease progression among individuals in this group. The rate of decline in CD4 counts among the mothers appears to be lower. It is speculated that either intensive exposure to sexually transmitted pathogens or infection with several strains of HIV-1 may account for the rapid disease progression among female sex workers.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:Individual cells capable of interferon-γ (IFN-γ) synthesis are easily detected by immunofluorescence and flow cytometric analysis using an anti–IFN-γ monoclonal antibody as specific reagent. By IFN-γ flow cytometry assay, we demonstrated that HIV-seropositive patients, starting at the early stage of viral infection, generally have an increased percentage of lymphocytes potentially able to produce IFN-γ, compared with healthy blood donors. IFN-γ expression in patient lymphocytes was observed to increase with the progressive stages of HIV infection, with the highest figures occurring in stage C patients. Such increased IFN-γ expression involved both CD4+and CD8+T cell subsets. Most interestingly, we found patients at the same stage of HIV infection who had similar numbers of total and CD4+lymphocytes but highly different percentages of lymphocytes potentially capable of producing IFN-γ.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID