Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review describes the potential role of oxidative stress as a cofactor of disease progression from asymptomatic human immunodeficiency virus (HIV) infection to the acquired immunodeficiency syndrome (AIDS). Oxidative stress is a known activator of HIV replication in vitro through the activation of a factor that binds to a DNA-binding protein, NF-kappa B, which in turn stimulates HIV gene expression by acting on the promoter region of the viral long terminal repeat. Tumor necrosis factor alpha (TNF-alpha), an essential cytokine produced by activated macrophages, is also involved in the activation of HIV infection through similar mechanisms. TNF-mediated cytotoxicity of cells exposed to this substance is related to the generation of intracellular hydroxyl radicals. An indirect argument in favor of the role of oxidative stress in HIV-associated disease progression is the consumption of glutathione (GSH), a major intracellular antioxidant, during HIV infection and progression. GSH is known to play a major role in regulation of T cell immune functions. Oxidative stress may also play an important role in the genesis of cellular DNA damage and, in this context, may be related to HIV-associated malignancies and disease progression. Finally, the role of antioxidants as components of therapeutic strategies to combat HIV disease progression is discussed.
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PMID:The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus. 164 Jan 66

As the focus of the management of human immunodeficiency virus (HIV) infection turns from the treatment of AIDS to the entire continuum of the disease, projection of long-term healthcare costs becomes increasingly important. Rather than a fulminant disease treated primarily inside the hospital, HIV infection will become a chronic condition requiring years of outpatient monitoring and pharmacologic intervention with attending increases in pharmacy costs. The objective of this study was to characterize outpatient drug costs by Walter Reed (WR) disease stage in order to estimate the association of disease progression and outpatient prescription drug costs. We hypothesized that there was an association between HIV disease progression, measured by the WR Staging Classification System, and outpatient prescription drug costs. Outpatient drug costs were summarized for 190 HIV-positive patients during a three-month period who presented at Walter Reed Army Medical Center for staging and follow-up. The overall median cost per day per patient for all stages was $3.21 (range $0.01-53.45) with wide variation between patients. Daily costs for patients in WR stage V were the greatest (median $9.26). There was a significant association between WR stage of disease and outpatient drug costs (Spearman rho = 0.51, t = 6.9, df = 188, p less than 0.001). The association was not completely linear because costs in WR stage VI were less than WR stages IV or V. Annual extrapolated outpatient drug costs for these 190 patients would be nearly $0.5 million.
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PMID:The relationship between outpatient drug costs and disease progression in the human immunodeficiency virus-infected population. The Military Medical Consortium for Applied Retroviral Research. 192 13

The acquired immune deficiency syndrome (AIDS) is a viral-induced disorder of humans that is reaching pandemic proportions. The etiologic agent responsible for AIDS is recognized as a retrovirus termed the human immunodeficiency virus (HIV). This virus is both cytotropic and cytopathic for T lymphocytes in vitro, and patients with AIDS and HIV-related conditions invariably have serious T cell abnormalities, notably a reduced number of the helper/inducer (CD4+) subpopulation. There is now a substantial body of evidence to suggest that the AIDS virus triggers a diverse range of autoimmune phenomena. The purpose of this article is to summarize the clinical and immunopathological manifestations of autoimmunity in HIV infection and to provide a perspective of the possible origins and roles autoimmune reactions play in HIV disease progression.
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PMID:AIDS virus infection and autoimmunity: a perspective of the clinical, immunological, and molecular origins of the autoallergic pathologies associated with HIV disease. 198 95

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

More than a million people in the United States are now infected with human immunodeficiency virus (HIV), and by 1991, the United States will record 270,000 cases of acquired immunodeficiency syndrome (AIDS). At present, there is no way to estimate the number of AIDS patients who will be living in 1991. Intestinal diseases exert considerable morbidity and mortality on AIDS patients and persons with AIDS-related complex. The elevated frequency of certain intestinal infectious diseases in homosexual male AIDS patients has been attributed to sexual practices, but food seems a probable vector for some proportion of the infections in all AIDS-affected groups. Intestinal infectious diseases and resulting systemic infections can be life-threatening to AIDS patients. The infections may serve as cofactors that hasten HIV disease progression to AIDS, but absolute proof of this hypothesis is lacking. The longer the HIV-infected person maintains good general health and avoids potentially lethal infectious diseases, the better are the chances that effective treatments will be developed and made available. Foodborne diseases are generally avoidable, and increased education of AIDS patients and their physicians as to their nature is the key to their prevention.
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PMID:Food counseling for persons infected with HIV: strategy for defensive living. 249 55

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

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

Studies examining specific antibodies directed against antigenic components of human immunodeficiency virus (HIV), as potential markers of progression to AIDS, have reported inconsistent results. We used reflectance densitometry and survival analysis to determine whether single quantitative measures of HIV-specific antibodies predicted progression to AIDS in a prospective cohort of 159 HIV-infected homosexual men. Lowered baseline levels of p24 antibody and p24/gp41 antibody ratio were independent predictors of progression to AIDS and retained statistical significance after simultaneously controlling for CD4:CD8 ratio, age, use of zidovudine, and clinical symptoms. Quantitative measures of p24 antibody and p24/gp41 antibody ratio warrant further study with regards to their clinical application as markers of HIV disease progression.
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PMID:Quantitative measures of human immunodeficiency virus-specific antibodies predict progression to AIDS. 759 82

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

A retrospective cohort study was conducted to analyze variables predictive of acquired immunodeficiency syndrome (AIDS), as defined by the Centers for Disease Control (CDC) in 1987, and death in 224 women infected with the human immunodeficiency virus (HIV) who were evaluated through two HIV outpatient programs in New Orleans between January 1987 and December 1991 and followed through February 1993. Variables predictive of AIDS in a multivariate proportional hazards model were an entry CD4 cell count < 200/mm3 (adjusted RR 8.2, 95% CI 3.2, 20.9) and rapid CD4 cell count decline (adjusted RR 6.0, 95% CI 2.4, 15.5). A baseline AIDS diagnosis (by the CDC 1987 definition) was highly predictive of death (RR 36.3, 95% CI 15.7, 70.1). In multivariate analyses none of the relative risks for predictive variables remained significant if adjusted for a diagnosis of AIDS at entry. Although immunological parameters were predictive of early HIV disease progression, an AIDS diagnosis was the strongest prognostic indicator of death in a cohort of North American women.
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PMID:Predictors of HIV disease progression in women. 771 34


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