Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a study of 75 alveolar cell co-cultures from 55 HIV-seropositive subjects, p24 antigen production was identified by ELISA in 11 out of 26 (42%) of unseparated cell cultures, 15 out of 39 (38%) purified alveolar macrophage cultures and eight out of 10 purified alveolar lymphocyte samples. Positivity in unseparated cell cultures was associated with an alveolar lymphocytosis greater than 30%. Negative macrophage cultures were significantly more likely in the early stages of HIV infection with none positive when the subject had a peripheral CD4+ cell count greater than 300/microliters. Alveolar macrophage infection thus appears to increase with HIV disease progression.
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PMID:HIV isolation from pulmonary cells derived from bronchoalveolar lavage. 204 30

A wide spectrum of immunomodulatory strategies offer promise for treating people with HIV infection; however, numerous gaps still exist in our understanding of the normal regulation of the immune system during the progression of HIV infection. Preclinical development of immunomodulators must include a strong rationale for the use of the immunomodulating substance substantiated by appropriate laboratory studies, in vitro as well as in vivo. Preclinical studies must demonstrate the safety of the proposed therapeutic agent, including an assessment of the potential for adverse effects on immune function and virus replication. Combined therapeutic modalities should also be appropriately evaluated at the preclinical level. Clinical evaluations should be instituted only after a strong rationale is substantiated and safety concerns are fully considered. Initial studies should be conducted with patients at an intermediate stage of HIV disease progression. Immunomodulators may exhibit unusual dose-response patterns, and this should be considered when designing the trials. The consultation recommended that WHO continue to provide a forum for the timely exchange and validation of information related to the development and clinical evaluation of immunomodulators for the treatment of individuals infected with HIV.
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PMID:Report of a WHO informal consultation on preclinical and clinical aspects of the use of immunomodulators in HIV infection. Geneva, 3-5 April 1989. World Health Organization Global Programme on AIDS. 208 96

The role of Epstein-Barr virus (EBV) on the progression of human immunodeficiency virus (HIV) infection is not well defined. The objective of this prospective study was to determine the prevalence of EBV excretion and the role that EBV might have on HIV disease progression. Fifty-two homosexual males were studied, all of whom had positive EBV serology. Twenty-four of the 27 HIV-seropositive and 14 of the 25 HIV-seronegative subjects had detectable levels of EBV DNA in oropharyngeal cells. In addition to a greater prevalence of detectable EBV, the level of excretion was higher among HIV-seropositives than among HIV-seronegatives, and higher among group III than among group II HIV-seropositive men. These results are consistent with earlier studies showing a relationship between immunosuppression and EBV reactivation. The EBV excretion levels in a control group of 52 age-matched heterosexual males were substantially lower than those found in the homosexual group. In a proportional hazards regression analysis EBV excretion was found to be the best single predictor of progression of HIV infection (P less than 0.001). HIV p24 core antigenemia (P = 0.048) and low EBNA (P = 0.024) were significant predictors independent of EBV excretion. Whether EV directly accelerates the time to progression or is merely a marker of underlying subclinical immunosuppression remains an open question.
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PMID:High levels of Epstein-Barr virus in the oropharynx: a predictor of disease progression in human immunodeficiency virus infection. 216 51

We have studied the sequence and function of the human immunodeficiency virus type 1 (HIV-1) nef genes from nine patients with highly divergent rates of disease progression enrolled in a longitudinal study of HIV disease. Over an average of 7.8 years of follow-up, three patients had net positive changes in CD4+ T-cell counts, three patients had net negative changes in CD4+ T cells but did not develop AIDS, and three patients progressed to AIDS. The nef gene from each of these patients was amplified and cloned, and the sequence of 8 to 10 clones was determined. Only 2 of 88 (2.3%) nef genes recovered from these nine patients were grossly defective. Moreover, there was no relationship between the phylogeny of nef sequences and the corresponding rates of disease progression from these patients. Representative nef genes from all nine patients were tested for their abilities to downregulate cell surface CD4 in a transient-transfection assay. There was no correlation found between the functions of the nef genes from these patients and their corresponding rates of disease progression. We conclude that the nef gene is not a common mediator of the rate of HIV disease progression in natural infection.
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PMID:Functional characterization of human immunodeficiency virus type 1 nef genes in patients with divergent rates of disease progression. 747 87

Employing a discontinuous Percoll gradient following Ficoll-Hypaque separation of peripheral blood mononuclear cells from normal subjects (n = 14) and patients with HIV-1 infection (n = 50), we separated a population of low-density cells consisting of monocytoid cells, lymphocytes, and some granulocytes. In cytospin preparations, less than 5% of the monocytoid cells were positive for nonspecific esterase and CD14. However, CD1a was positive in 5-20% of these cells. Ultrastructurally, CD1a-labeled immunogold particles were demonstrated on the monocytoid cells which bore some features of dendritic cells. Flow cytometry of the low-density cells identified a subset of buoyant, large cell population, which excluded lymphocytes. This large low-density cell (LLDC) population was significantly expanded in patients with HIV infection and comprised 32.3 +/- 21.3% of low-density cells compared to 7.0 +/- 2.8% in normal subjects (P < 0.0001). Of the LLDC population 45.2 +/- 23.4% were CD1a+ in patients compared to 17.5 +/- 13.3% in normal subjects (P < or = 0.0001). HLA-DR and HLA-DQ were coexpressed in approximately 70 and 50% of these CD1a+ LLDC, respectively. A simple nonculture assay method employed by us facilitates rapid screening of infected blood specimens for the CD1a+ large low-density cells with dendritic cell features, which could be an additional parameter to monitor HIV disease progression.
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PMID:The number of CD1a+ large low-density cells with dendritic cell features is increased in the peripheral blood of HIV+ patients. 750 34

We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4+ or CD8+ phenotype ('blind' T-cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident human immunodeficiency virus, type 1 (HIV-1), infection who remained free of acquired immunodeficiency syndrome (AIDS) for up to eight years after seroconversion. In contrast, seroconverters who developed AIDS exhibited rapidly declining T cells (both CD4+ and CD8+) for approximately two years before AIDS, independent of the time between seroconversion and AIDS, suggesting that homeostasis failure is an important landmark in HIV disease progression. Given the high rate of T-cell turnover in HIV-1 infection, blind T-cell homeostasis may contribute to HIV pathogenesis through a CD8+ T lymphocytosis that interferes with regeneration of lost CD4+ T cells.
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PMID:Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. The Multicenter AIDS Cohort Study. 758 34

Zidovudine remains the mainstay in the treatment of patients infected with human immunodeficiency virus (HIV). The drug delays disease progression to acquired immunodeficiency syndrome (AIDS) and to AIDS-related complex (ARC), reduces opportunistic infections, and increases survival in patients with advanced HIV infection. There is evidence to suggest that zidovudine also delays disease progression in patients with mild symptomatic disease. Although one study has shown zidovudine to have no significant beneficial effects on survival or disease progression in patients with asymptomatic HIV infection, several other studies have shown zidovudine to delay disease progression in this patient group. Results from related ongoing studies are awaited with interest. Zidovudine reduces the incidence of AIDS dementia complex (ADC) and appears to prolong survival in these patients, and improves other neurological complications of HIV infection. The drug also appears to enhance the efficacy of interferon-alpha in patients with Kaposi's sarcoma. Although zidovudine is widely used as postexposure prophylaxis following accidental exposure to HIV, its efficacy in preventing seroconversion is unclear. Whether zidovudine prevents vertical transmission also remains to be determined. The overall efficacy of zidovudine in the treatment of children with HIV infection appears similar to that in adults despite more rapid disease progression in younger patients. Zidovudine-resistant isolates can emerge as early as after 2 months' therapy, and primary infection with zidovudine-resistant strains has been documented. Both zidovudine resistance and the syncytium-inducing HIV phenotype appear to be associated with poor clinical outcome. However, zidovudine resistance may revert on drug withdrawal or switching to an alternative therapy. Zidovudine-associated haematotoxicity may be dose-limiting. Nonhaematological adverse events associated with zidovudine therapy are generally mild and usually resolve spontaneously. Dosages of approximately 500 to 600 mg/day appear to be at least as effective as dosages of 1200 to 1500 mg/day and are better tolerated in patients with less advanced disease. However, optimal dosage are unclear. Despite beneficial effects, zidovudine monotherapy is not curative. There is evidence to suggest that the concomitant administration of zidovudine with didanosine or zalcitabine is effective in patients with HIV disease progression despite receiving zidovudine monotherapy, and there is some evidence that concomitant zidovudine plus didanosine therapy is more effective than alternating monotherapy. However, results from studies of combination therapy in asymptomatic patients, and from comparative combination therapy studies are awaited. Cotherapy with agents that augment haematopoiesis allows the continuation of therapeutic zidovudine dosages.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Zidovudine. An update of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. 2863 41

Previous studies demonstrated that mucosal HIV p24 antigen content varied during the progression of HIV infection. In this study, expression of HIV RNA and mRNA of selected cytokines was examined in rectal mucosa from HIV-infected individuals. Rectal biopsies from 27 subjects were studied: 7 with CD4 counts > 500/mm3 (early), 11 with CD4 < 500 (intermediate), and 9 with AIDS (late), plus 4 HIV-seronegative controls. RNA in situ hybridization was performed using 35S-labeled riboprobes of HIV, TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, INF-alpha, IFN-gamma, and TGF-beta. HIV RNA was detected more frequently in the intermediate group than in the other groups (p < 0.005). Cytokine mRNA expression also varied during disease progression. The expression of IFN-alpha, IFN-gamma, and TGF-beta mRNA was most prevalent early in the disease; peak expression of IL-4, IL-5, IL-6, and IL-10 was seen during the intermediate stage, and peak expression of TNF-alpha and IL-1 beta mRNA were seen in AIDS patients. HIV RNA and cytokine mRNA expression vary during HIV disease progression. HIV RNA expression is greatest in the intermediate stage of the disease. The pattern of cytokine mRNA expression suggests predominant cell-mediated immunity under basal conditions and early in the disease, generalized cytokine activation in its middle phase, and proinflammatory cytokine activation in AIDS patients. Cytokine modulation of HIV expression in rectal mucosa in vivo may occur and have pathogenic importance.
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PMID:Variation in the expression of human immunodeficiency virus RNA and cytokine mRNA in rectal mucosa during the progression of infection. 770 12

Of the Edinburgh cohort of approximately 130 children born to HIV-infected women, 9 are infected and alive. This article describes results from the first 18 months of a natural history study of seven of these, and two adopted children, studying the CD8 T cell-mediated cytotoxicity against HIV proteins (Gag, Tat, Pol, and Env), over time, and relating it to clinical progression and viral activity. Autologous EBV cell lines infected with vaccinia-HIV constructs were used as target cells, and bulk-cultured peripheral blood mononuclear cells as effector cells. The children ranged in age from 0 to 93 months, with six of the nine showing CTL activity to one or more HIV proteins. The specificity of the response was directed against Tat in the younger children, switching to Pol, then Gag or Env. Preliminary analysis of virological data showed no association between CTL and virus activity. The children with CTLs tended to be well clinically, but the cohort needs to be studied longer before conclusions can be made about CTL activity and HIV disease progression. Cytotoxic T lymphocyte activity has also been observed in two children diagnosed as HIV uninfected. These results show the importance of looking at CTL specificity, and may have implications in vaccine design.
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PMID:Cytotoxic T lymphocyte activity in children infected with HIV. 786 39

Hepatitis A vaccination has been recommended to patients with hemophilia since they are exposed to potentially infectious clotting factor concentrates. Aim of this study was to assess the immunogenicity of vaccination in hemophiliacs, infected or not with the human immunodeficiency virus (HIV). A formalin-inactivated hepatitis A vaccine was injected subcutaneously to 113 susceptible adults and children and repeated after 1 and 6 months. 47 vaccinees were anti-HIV positive (28 asymptomatic, 15 with CD4 cell counts of less than 200/microliter and 4 with symptomatic disease). The first dose of vaccine induced seroconversion, with antibody titers of at least 20 mIU/ml, in 89% of the 66 anti-HIV negative patients, 100% of them responding after the second injection. In anti-HIV positive hemophiliacs seroconversion rates and antibody titers were significantly lower than in non-infected patients. After 12 months, only 76% of anti-HIV positive vaccinees and 40% of those with signs of HIV disease progression maintained the antibody, whereas all anti-HIV negative patients had titers of 20 mIU/ml or more. Our results indicate that there is an association between defective response to hepatitis A vaccine and stage of progression of HIV disease.
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PMID:Patterns of immunogenicity of an inactivated hepatitis A vaccine in anti-HIV positive and negative hemophilic patients. 787 24


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