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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 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.
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PMID:The use of hematopoietic growth factors in HIV infection and AIDS-related malignancies. 171 6

Previously we raised a rabbit monospecific antibody (C2003) against a synthetic peptide derived from a sequence within the C-terminal portion of the reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1). This sequence is found to be conserved in the predicted amino acid sequence of a related lentivirus, the equine infectious anemia virus (EIAV). It was previously determined that the C2003 antibody could cross-react with native EIAV RT and directly inhibit the DNA polymerase activity of the enzyme. We have now fractionated EIAV RT by immunoaffinity chromatography with immobilized C2003 antibody. The procedure yielded an equimolar mixture of two proteins of 66 and 51 kDa associated with both DNA polymerase and RNase H activities. When the EIAV RT proteins were examined by in situ activity gel assays, polymerase activity was found to be principally associated with the 66-kDa component. The fidelity of DNA synthesis by EIAV RT was found to be equivalent to that of HIV-1 RT and lower than that of AMV RT. These observations indicate that the RTs of EIAV and HIV-1 share similar structural and functional properties.
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PMID:Purification and partial characterization of equine infectious anemia virus reverse transcriptase. 171 86

Hematopoietic dysfunction with peripheral cytopenias is a common complication of human immunodeficiency virus (HIV) infection. Symptomatic anemia is the most common cytopenia and occurs in the presence and absence of myelosuppressive drug therapy such as zidovudine. Drug-induced neutropenia and immune thrombocytopenia are also frequent and occur in up to 50% of acquired immunodeficiency syndrome (AIDS) patients. Attempts to reduce the impact of bone marrow failure have focused on dose reduction of zidovudine, ganciclovir, and chemotherapy, and the use of recombinant hematopoietic hormones such as erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF). Despite these maneuvers, approximately 30% of patients with AIDS receiving zidovudine will become transfusion-dependent. This has led to investigations of other cytokines that may increase blood cell formation. The recent identification of decreased number and proliferation of hematopoietic progenitors in patients with HIV infection suggests that agents which have activity on progenitor cell pools may have clinical utility. We demonstrate that human stem cell factor (HuSCF) increases burst-forming unit-erythroid (BFU-E), colony-forming unit-granulocyte-monocyte (CFU-GM), and CFU-Mix formation in vitro in normal and HIV-infected individuals. HuSCF also decreases the sensitivity of BFU-E to inhibition by zidovudine without altering HIV replication in lymphocytes or monocytes, altering peripheral blood mononuclear cell proliferation to phytohemagglutinin (PHA) and interleukin-2 (IL-2) or altering the effectiveness of zidovudine or dideoxyinosine in inhibiting HIV replication in lymphocytes or monocytes. These studies suggest that HuSCF may have clinical utility in HIV infection as an adjunctive treatment for HIV-related cytopenias.
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PMID:Potential use of human stem cell factor as adjunctive therapy for human immunodeficiency virus-related cytopenias. 172 Jun 98

Human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) were purified by sucrose density gradient centrifugation in the presence of 1 mM EDTA. Pelleted gradient fractions were analyzed for total protein, total Gag capsid protein, and total zinc. Zinc was found to copurify and concentrate with the virus particles. Through successive cycles of resuspending in buffer containing EDTA and repelleting, the zinc content remained constant at about 1.7 mol of zinc per mol of Gag protein. Proteins from purified virus (HIV-1 and HTLV-I) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted to polyvinylidene fluoride paper, and probed with 65ZnCl2. Viral nucleocapsid (NC) proteins (HIV-1 p7NC and HTLV-I p15NC) bound 65Zn2+. Other retroviruses, including simian immunodeficiency virus, equine infectious anemia virus, bovine leukemia virus, Moloney murine leukemia virus, mouse mammary tumor virus, and Mason-Pfizer monkey virus, were found to contain amounts of zinc per milligram of total protein similar to those found in HIV-1 and HTLV-I. Collectively, these data support the hypothesis that retroviral NC proteins function as zinc finger proteins in mature viruses.
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PMID:Tightly bound zinc in human immunodeficiency virus type 1, human T-cell leukemia virus type I, and other retroviruses. 173 Nov 11

In a series of 342 bone marrow examinations from 314 patients with human immunodeficiency virus infection, 70 examinations (20%) detected opportunistic mycobacterial or fungal infections. One hundred eleven of the 314 patients had such infections, and, hence, 63% (70/111) were detected by bone marrow examination. Special stains for microorganisms detected 16 (32%) of 50 Mycobacterium avium complex infections, 10 (22%) of 45 Mycobacterium tuberculosis infections, eight (73%) of 11 Histoplasma capsulatum infections, and five (83%) of six Cryptococcus neoformans infections. Bone marrow cultures detected 36 (72%) of the 50 M avium complex infections, 13 (29%) of the 45 M tuberculosis infections, and 63% of the fungal infections. Marrow examination revealed infection in only one of the 70 specimens (1%) collected to evaluate thrombocytopenia alone or hematologic malignancy, but in 69 (25%) of 274 with fever, neutropenia, anemia, or miscellaneous other indications for marrow examination. Granulomas were detected in 102 (30%) of the biopsy specimens, including 71 (64%) of those in cases with mycobacterial or fungal infection. The granulomas showed caseous necrosis in nine cases, all in patients with tuberculosis, and the 27 cases with tuberculosis-associated granulomas tended to show large, tightly cohesive granulomas. The presence of granulomas correlated with opportunistic infection in 82 (80%) of 102 cases. Without granulomas, special stains were positive in only eight (3%) of 240 specimens. These results suggest that (1) bone marrow granulomas are a common and valuable histologic clue to opportunistic infection; (2) without them, special stains may not be a cost-efficient way to diagnose such infection; and (3) bone marrow examination can be a useful method of diagnosing opportunistic mycobacterial and fungal infections in patients with fever, anemia or neutropenia, and underlying human immunodeficiency virus infection.
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PMID:Bone marrow examination for the diagnosis of mycobacterial and fungal infections in the acquired immunodeficiency syndrome. 174 30

The natural history of HIV infection continues to change with improved diagnostic and therapeutic modalities available to manage opportunistic infections and malignancies. Antiretroviral therapy with zidovudine and other investigational agents has improved the median survival of AIDS patients from 11 months in 1985 to 18-25 months at present. Most importantly, early intervention with zidovudine can delay onset of clinical illness in asymptomatic patients and progression to AIDS in symptomatic patients. A 500 mg/d dose has been found as effective as previously recommended doses of 1200-1500 mg/day. Lower doses decrease the incidence and severity of adverse effects and therapeutic benefit appears to be greatest in asymptomatic patients with CD4 lymphocyte counts less than 500/ul. Indications for zidovudine, therefore, have been expanded to include asymptomatic adults with CD4 lymphocyte counts less than 500/ul. Concerning early intervention with zidovudine, studies were not designed to measure survival or define the optimal timing of intervention based on immunologic status. In addition, long-term benefits are not clearly defined, particularly since the drug seems to lose clinical effectiveness after approximately two years, probably due to emergence of resistant HIV strains. Adverse effects continue to occur even at low doses including headaches, nausea, anemia and neutropenia, myopathy and possible hepatitis. Nevertheless, the overall clinical benefit seems to be greatest, albeit temporary, in asymptomatic patients. The optimal dosage appears to be 500-600 mg/d; however, this may not be sufficient for infection in the central nervous system.
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PMID:Management of HIV infection in adults. 175 30

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.
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PMID:Erythropoietin. Biology and clinical applications. 178 66

Fungal infections in humans are provoked and exacerbated by defects in the cellular immune system. Hence, the emergence of novel clinical variants of oral candidoses and rare mycoses with the pandemic spread of human immunodeficiency virus infection is not surprising. The new clinical entities of oral candidoses that have been described in the past few years have had a significant impact on the classification of these diseases. Classification of oral candidoses is an issue addressed in some detail here. Angular cheilitis is a disease commonly associated with Candida infection. In the West, it is frequently seen in the elderly, but a report from Asia indicates that the disease may be prevalent in the young age groups due to factors such as anemia, despite the similarity of the infective agents. A novel cofactor implicated in infectious states has been the host blood group secretor status, and data from three studies suggest that the latter may play an intriguing role in the pathogenesis of oral candidosis. Finally, a new mouse model has been described as a substitute for the rat model in investigating the host-parasite interactions in oral candidosis, and its pros and cons are reviewed.
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PMID:Superficial oral fungal infections. 180 1

In progressive stages of infection with human immunodeficiency virus type 1 (HIV-1), the majority of patients develop a pathophysiologically not yet completely explainable bone marrow failure with anemia, leukopenia, and thrombocytopenia. The clinically most widely used HIV-inhibiting antiviral drugs azidothymidine (AZT) and dideoxyinosine (ddI) frequently are hematotoxic to the host, resulting in dose reduction or discontinuation of antiviral therapy. In recent studies, a novel series of benzodiazepine derivatives highly active against HIV-1 was synthesized. These antiviral compounds have a much more favorable therapeutical index than the well-known 2'3'-dideoxyribosides, like AZT. In the experiments presented here, the authors investigated the most promising derivative R82913 [(+)-S-4,5,6,7-tetrahydro-9-chloro-5-methyl- 6-(3-methyl-2-butenyl)-imidazo[4,5,1-jk] [1,4]-benzodiazepin-2(1H)-thione] (TIBO) with regard to its toxicity on bone marrow-derived hematopoietic progenitor cells from six HIV-1+ and HIV- persons, respectively. In methylcellulose assays for hematopoietic colony growth any hematotoxic effects of R82913 in vitro were excluded, as both groups showed no difference of progenitor cell growth with or without the TIBO derivative, even at concentrations 6.7 x 10(4) times higher than the 50% inhibitory concentration for cytopathicity by HIV-1.
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PMID:TIBO R82913, a new HIV-1 inhibiting agent, does not inhibit hematopoietic progenitor cells. 181 43

The antiretroviral activity, tolerance and toxicity of two different antiviral drug combinations were assessed and compared in a randomized, crossover pilot study in 16 HIV-1 p24 antigenaemic subjects with asymptomatic HIV infection. Oral zidovudine 250 mg twice daily was combined with either oral acyclovir 800 mg twice daily or lymphoblastoid interferon-alpha 1.5 x 10(6) IU administered subcutaneously three times weekly. The 12-week treatment period was followed by a 4-week washout period and a further 12-week crossover phase. During the entire treatment period a decline in p24 antigen was observed in all patients. No significant differences were found between the two treatment regimens. No patient showed clinical progression of HIV infection. Three patients were withdrawn from the study, one due to serious anaemia and two due to severe clinical adverse events. Long-term efficacy and tolerance data in asymptomatic HIV-infected patients with these regimens would be valuable.
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PMID:Low-dose zidovudine in combination with either acyclovir or lymphoblastoid interferon-alpha in asymptomatic HIV-infected patients: a pilot study. 181 9


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