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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus (HIV) infection causes a number of clinical syndromes and many laboratory abnormalities, often heralding the development of the life-threatening opportunistic infections or malignancies that are known as the acquired immunodeficiency syndrome (AIDS). Drawing heavily on the results of prospective cohort studies, particularly those that my colleagues at the National Cancer Institute and I have conducted, this paper reviews the relationship of AIDS to clinical signs and symptoms, immunologic measures, and viral assays. The risk of AIDS in the next 3 years is at least 25 to 50% for HIV-infected subjects who have oral candidiasis, unexplained fever, unexplained weight loss, a CD4+ lymphocyte count below 200 cells/microliter, or combinations of these. Elevated serum levels of beta 2 microglobulin and neopterin also appear to be strong predictive markers of AIDS, but further work is needed in diverse HIV-infected populations, such as intravenous drug users and persons in pattern II countries, such as Haiti and central Africa. Elevated levels of interferon or HIV-p24 antigen in the serum are insensitive but highly specific AIDS markers that may have predictive value independent of CD4 lymphocyte levels. Several potentially valuable immunologic (immunoglobulin levels, tumor necrosis factor, soluble interleukin 2) and virologic (HIV viremia) assays remain to be thoroughly evaluated or technically simplified. Data from prospective cohort studies have provided clinical and laboratory markers of AIDS risk that have proved essential for therapeutic trials and other clinical decisions. As effective treatments for HIV infection and its complications begin to emerge, these marker data will also prove invaluable for mathematic modeling of the scope, course, and public health response to the epidemic.
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PMID:Prognostic markers for AIDS. 166 94

The widespread prevalence of Kaposi's sarcoma during the HIV/AIDS epidemic and its unique epidemiological predilection for select groups 'at risk' for AIDS relative to their 'life-style' orientation provide the rationale for etiologic agent(s) other than HIV. In keeping with the requisites for the development and progression of malignancy, i.e., the transformation of normal to aberrant cells and the failure of host defenses to control them, is the rationale, in view of their respective properties, for the hypothesized participation of spermatozoa and/or seminal fluid components as being contributory to the development of Kaposi's sarcoma.
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PMID:The persisting enigma of AIDS-associated Kaposi's sarcoma: a hypothesis. 166 80

Dehydroepiandrosterone (DHEA) and its interconvertible sulfate derivative (DHEA-S) are human androgenic steroids that have been reported to inhibit viral expression and have been associated with a decreased risk of cancer. The relationship between serum DHEA and DHEA-S levels and subsequent progression to AIDS was investigated in a sample of human immunodeficiency virus (HIV)-infected men from the San Francisco Men's Health Study followed prospectively since 1984. Among 108 men seropositive for HIV at study entry and with CD4 lymphocyte counts of 200-499 microliters 24 months later, serum DHEA levels below the lower limit of normal (less than 180 ng/dl) at this later date were predictive of subsequent progression to AIDS (relative hazard = 2.34; 95% confidence interval = 1.18-4.63; P = .01) after controlling for hematocrit, age, and log absolute CD4 cell number in a Cox proportional hazards model. This is the first large prospective cohort in which an endocrinologic variable has been observed to independently predict progression to AIDS. These observations, in addition to recent in vitro data, suggest that DHEA might have a protective effect in HIV infection.
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PMID:Decreased serum dehydroepiandrosterone is associated with an increased progression of human immunodeficiency virus infection in men with CD4 cell counts of 200-499. 168 93

To determine the true incidence of abnormalities in bone marrow specimens from patients infected with human immunodeficiency virus (HIV) and the clinical significance of these abnormalities regarding their cause and their role in the production of hematologic complications, 216 bone marrow biopsies, aspirates, and/or imprint preparations from 178 patients who either were seropositive for HIV infection or met the Centers for Disease Control (CDC) criteria for acquired immunodeficiency syndrome (AIDS) were studied. Detailed morphologic review was performed in a blind fashion as to clinical status. Extensive clinical, therapeutic, and laboratory data were collected for each patient. Statistical analysis was performed to detect significant correlations between morphologic findings and clinical/therapeutic/laboratory features. Among the most common bone marrow findings were hypercellularity (53% of specimens), myelodysplasia (69%), evidence of reticuloendothelial (RE) iron blockade (65%), megaloblastic hematopoiesis (38%), fibrosis (20%), plasmacytosis (25%), lymphocytic aggregates (36%), and granulomas (13%). A number of statistically significant correlations between morphologic findings and clinical features were noted. No significant association was detected between any morphologic finding and therapy with a variety of drugs. In 7 of 14 (50%) patients found to have marrow involvement by malignant neoplasm, the bone marrow represented the initial site of diagnosis of the neoplasm. Most of the bone marrow abnormalities associated with HIV infection appear to be related directly to the infection or its complications and not to therapeutic intervention. In certain clinical situations, bone marrow examination continues to be useful in the management of patients infected with HIV.
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PMID:The bone marrow in human immunodeficiency virus (HIV)-related disease. Morphology and clinical correlation. 170 27

A recombinant plasmid carrying the long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1) linked to the reporter chloramphenicol acetyl transferase (CAT) gene was stably introduced into rat liver cells. The transfectant cells expressed CAT activity from the HIV LTR. The response to doxorubicin was studied and it was found that at the optimum concentration of 20 micrograms/ml doxorubicin, the expression of CAT from the HIV LTR was stimulated by 65-fold. Our results suggest caution against therapy including doxorubicin in the treatment of AIDS patients.
Cancer Lett 1991 Feb
PMID:Doxorubicin stimulates transcription from the human immunodeficiency virus long terminal repeat sequences. 170 76

Pentoxifylline (Trental), used routinely for the treatment of intermittent claudication, has been shown previously to decrease the levels of tumor necrosis factors-alpha (TNF-alpha) RNA in cancer patients and to lead to a general improvement of well being. Increased TNF-alpha levels have been observed not only in cancer patients but also in cachectic patients with the acquired immunodeficiency syndrome (AIDS), and TNF-alpha is known to increase the expression of the human immunodeficiency virus type 1 (HIV-1) via activating its long terminal repeat (LTR). Moreover, TNF-alpha decreases the therapeutic efficacy of zidovudine (AZT). Here we show a significant decrease in HIV-1 replication by pentoxifylline in infected human peripheral blood mononuclear cells. The reduction was proportional to the downregulation of expression of a reporter gene, the bacterial gene for chloramphenicol acetyl transferase, linked to the HIV-1 LTR in human monocytoid cells. We conclude that patients with AIDS may benefit from pentoxifylline treatment because of its blockage of TNF-alpha-mediated HIV-1 upregulation, from increased efficacy of AZT, and also from improvement in TNF-alpha-induced cachexia.
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PMID:Pentoxifylline (Trental) decreases the replication of the human immunodeficiency virus type 1 in human peripheral blood mononuclear cells and in cultured T cells. 130 72

Human immunodeficiency virus (HIV) infection is associated with multiple defects in immune regulation and hematopoiesis. These defects include decreased proliferation of hematopoietic progenitor cells and increased destruction of mature cells. There are also disturbances of regulatory cytokines. As a result, hematopoietic cytopenias are common and the tolerance of myelosuppressive therapy is poor. One successful approach to the management of these clinical problems is the use of hematopoietic growth factors. To date, three agents have been studied in patients with HIV infection. In a Phase I trial, granulocyte macrophage-colony stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, alpha-interferon, and antineoplastic therapy. In a placebo-controlled trial, erythropoietin (EPO) decreased transfusion requirements and corrected anemia in the majority of patients receiving zidovudine. In a Phase I/II trial, granulocyte colony-stimulating factor (G-CSF) also corrected leukopenia and neutrophil defects in patients with AIDS without altering HIV expression. Combined G-CSF and EPO treatment corrected both anemia and leukopenia and reduced zidovudine toxicity. New combinations of hematopoietic stimulants are being used to decrease the toxicity from cytotoxic chemotherapy in the treatment of AIDS-related malignancies. Future treatments with other recombinant cytokines may result in both reduction in myelosuppression from drug therapy and, possibly, reconstitution of the immune and hematopoietic systems of HIV-infected patients.
Cancer Invest 1991
PMID:The use of hematopoietic growth factors in HIV infection and AIDS-related malignancies. 171 6

Biliverdin (BV) is a bile pigment having anti-allergic properties. We examined the effect of BV on human immunodeficiency virus type 1 (HIV-1) in vitro. BV completely inhibited the cytopathic effect of HIV-1 in MT-4 cells at concentrations of 22.2 micrograms/ml or more. This inhibitory effect was also observed when BV was present during the adsorption period of HIV-1. However, BV was cytotoxic to MT-4 cells at concentrations above 800 micrograms/ml. At a concentration of 66.7 micrograms/ml, BV completely inhibited syncytia formation by HIV-infected and uninfected MOLT-4 cells. Moreover, after exposure of HIV-1 particles to BV for 2 h, the infectivity of the virus was reduced in a dose-dependent manner. It is speculated that the anti-HIV activity of BV is due to direct inactivation of virions and inhibition of virus binding to target cells.
Jpn J Cancer Res 1991 Jul
PMID:In vitro anti-human immunodeficiency virus type 1 activity of biliverdin, a bile pigment. 171 37

We are implementing a series of complementary assays for initial follow-up confirmation and prioritization of new active anti-HIV compounds identified by the U.S. National Cancer Institute's large-scale in vitro primary anti-HIV screen. Two different kinds of cellular viability assays, in addition to specific assays for total cellular DNA content, supernatant reverse transcriptase activity, p24 core antigen production and the synthesis of infectious HIV virions are all performed from a single well of a 96-well microtiter plate containing human host cells infected with HIV. Antiviral activities of several known prototype HIV inhibitors including 3'-azido,3'-deoxythymidine, 2',3'-dideoxycytidine, dextran sulfate and phorbol myristate acetate were compared in these multiparameter assays as a means of validation. Procedures to automate the method optimally, as well as to maximize the safety of the technicians working with HIV and HIV-infected cells have been emphasized. The resulting semiautomated, highly reproducible battery of assays yields a maximum amount of antiviral and cytotoxicity information from a minimum amount of sample. This is especially crucial when analyzing new synthetic compounds and natural product extracts or fractions where the available amounts of sample may be very limited.
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PMID:A semiautomated multiparameter approach for anti-HIV drug screening. 171 15

Tryptophan (Trp) is an indispensable amino acid required for biosynthesis of proteins, serotonin and niacin. Indoleamine 2,3-dioxygenase (IDO) is induced by infections, viruses, lipopolysaccharides, or interferons (IFNs) and this results in significant catabolism of Trp along the kynurenine (Kyn) pathway. Intracellular growth of Toxoplasma gondii and Chlamydia psittaci in human fibroblasts in vitro is inhibited by IFN-gamma and this inhibition is negated by extra Trp in the medium. Similarly, growth of a number of human cell lines in vitro is inhibited by IFN-gamma and addition of extra Trp restores growth. Thus, in some in vitro systems, antiproliferative effects of IFN-gamma are mediated by induced depletion of Trp. We find that cancer patients given Type I or Type II IFNs can induce IDO which results in decreased serum Trp levels (20-50% of pretreatment) and increased urinary metabolites of the Kyn pathway (5 to 500 fold of pretreatment). We speculate that in vivo antineoplastic effects of IFNs and clinical side effects are mediated, at least in part, by a general or localized depletion of Trp. In view of reported increases of IFNs in autoimmune diseases and our earlier findings of elevated urinary Trp metabolites in autoimmune diseases, it seems likely that systemic or local depletion of Trp occurs in autoimmune diseases and may relate to degeneration, wasting and other symptoms in such diseases. We find high levels of IDO in cells isolated from synovia of arthritic joints. IFNs are also elevated in human immunodeficiency virus (HIV) patients and increasing IFN levels are associated with a worsening prognosis. We propose that IDO is induced chronically by HIV infection, is further increased by opportunistic infections, and that this chronic loss of Trp initiates mechanisms responsible for the cachexia, dementia, diarrhea and possibly immunosuppression of AIDS patients. In these symptoms, AIDS resembles classical pellagra due to dietary deficiency of Trp and niacin. In preliminary studies, others report low levels of Trp and serotonin, and elevated levels of Kyn and quinolinic acid in AIDS patients. The implications of these data in cancer, autoimmune diseases and AIDS are discussed.
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PMID:Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. 172 46


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