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

The first placebo-controlled trial of zidovudine in the management of HIV infection involved patients with the acquired immune deficiency syndrome (AIDS) following their first episode of Pneumocystis carinii pneumonia and patients with severe AIDS-related complex (ARC). Zidovudine was shown to increase survival, and the trial was terminated early at the request of an independent review board. In order to obtain more information on the long-term efficacy and tolerance of the drug the study was continued on an open-label basis where all patients were offered zidovudine. Data from this ongoing open-label study are reviewed on a regular basis. Side-effects associated with zidovudine include anaemia and neutropenia both of which are more predominant in patients with more advanced disease. Two basic strategies have been adopted with the aim of improving the therapeutic index of the drug involving (i) dose modification and (ii) combination with other antiviral or immunomodulatory compounds. Although several phase I and II studies are proceeding it is likely that research in this area will continue to expand. AIDS patients with Kaposi's sarcoma (but without a history of AIDS-defining opportunistic infection) were precluded from the original phase II trial described above. The value of zidovudine in the treatment of the sarcoma per se has yet to be established. Trials are currently in progress in this indication evaluating the potential of zidovudine administered either alone or in combination with interferon. Possibly the largest area of research is concerned with defining the role of zidovudine earlier in the course of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Current and future trials with zidovudine. 264 66

Treatment of the acquired immunodeficiency syndrome with 3-azidothymidine (zidovudine; AZT) can induce severe neutropenia and anemia, while platelet counts increase. In order to understand the mechanism by which this favorable effect on platelets is induced, we prospectively studied platelet kinetics and platelet serology in 8 hemophiliacs receiving the drug. All patients underwent a second investigation after 3 months of treatment. Four patients were thrombocytopenic before treatment. Platelet counts increased significantly already after 1 week of treatment (p = 0.03), when only 3 patients remained thrombocytopenic. In these latter patients a further increase of platelet counts was noticed during the following 3 months. Platelet life-span was shortened in all patients at the initial investigation and a significant prolongation was measurable at the second evaluation (p = 0.015). Platelet-associated immunoglobulin G was increased in 3 patients at the first investigation and in 4 patients at the follow-up. Platelet-associated complement (PAC3d) was elevated in all subjects at the first determination. It decreased in 6, but increased in 2 patients thereafter; thus these changes did not become significant (p = 0.078). Immunofluorescence studies revealed antiplatelet antibodies in 7 patients' sera before treatment, and in 5 sera during drug therapy. At both investigations, the antibodies bound to the platelet glycoprotein IIIa as was demonstrated by immunoprecipitation of radiolabeled platelet proteins. We conclude, that AZT treatment improves platelet counts in HIV-infected hemophiliacs primarily by a prolongation of platelet survival without having a significant influence on antiplatelet antibody binding.
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PMID:Effects of 3-azidothymidine on platelet counts, indium-111-labelled platelet kinetics, and antiplatelet antibodies. 267 61

We report our experience of peripheral blood and bone marrow changes in patients with HIV disease. Abnormalities were most commonly seen in patients with advanced disease. In AIDS group IV patients (CDC classification) anaemia (92%) neutropenia (85%) monocytopenia (75%) and thrombocytopenia (61%) have their highest incidence, the reason being a combination of factors such as infection, myelosuppressive drugs and HIV infection itself. Bone marrow examinations were performed most commonly for microbiological culture (25%) and the investigation of anaemia (16%). Morphological changes in the bone marrow were non-specific and not pathognomic; however erythroid hypoplasia was found to be a distinctive feature associated with MAI infection. The procedure provided a high yield for microbiological culture, particularly in MAI infection.
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PMID:HIV-disease and bone marrow changes: a study of 60 cases. 272 58

Azidothymidine (AZT) is a useful drug in management of AIDS. Nevertheless, its hematologic toxicity such as anemia and neutropenia present further complications to an already compromised hematopoietic state in patients. We studied the effects of AZT on human and murine bone marrow (BM) colony growth as determined by assays of CFU-E, BFU-E, CFU-GM, and fibroblastoid stromal (CFU-Fb) colonies. Cultures were grown in methylcellulose with growth factors and scored after three- to 14-day incubation. In general, murine marrow cultures were more sensitive to AZT as compared with human marrow. Furthermore, interindividual variation in toxicity to AZT was observed between marrow samples; 1 mumol/L AZT inhibited murine CFU-E, BFU-E, and CFU-GM by 98% to 100%, whereas human marrow was inhibited by 52%, 87%, and 65%, respectively. Lower concentrations of AZT (0.1 mumol/L) inhibited murine erythroid colony growth by 85% to 90%, whereas human growth was inhibited by only 39% to 52%. Myeloid colony inhibition was similar for human and murine systems. CFU-Fb growth was markedly suppressed (75%) by 1 mumol/L AZT. Hemin, at a concentration of 10 mumol/L, overcame some of the inhibitory effects of 1 to 0.1 mumol/L AZT without hindering antiviral activity. Inhibition of human CFU-E growth was completely overcome with hemin, whereas CFU-GM growth was recovered to 66% to 74% of control. A similar but less pronounced effect was observed for BFU-E. Furthermore, hemin does not decrease AZT's effects of HIV antigen content in vitro. We conclude that anemia and neutropenia, occurring as a result of AZT, may not be as pronounced in the presence of hemin. Furthermore, CFU-Fb was significantly reduced in the presence of low concentrations of AZT. This may indicate a major target site for BM toxicity since the stromal microenvironment may be responsible for maintaining short- and long-term hematopoiesis.
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PMID:Microenvironmental toxicity of azidothymidine: partial sparing with hemin. 275 5

Recovery of bone marrow function in aplastic anemia patients treated with immunosuppressive therapy first suggested a role for the immune system in bone marrow failure. High recovery rates in patients treated with immunosuppressive therapy suggested that an immune mechanism may be a final common pathway of marrow failure in this disease. In vitro studies have shown that aplastic peripheral blood and marrow cells and their supernatants are capable of suppressing hematopoiesis by autologous and normal marrow. Soluble factors identified in this system include gamma interferon and lymphotoxin. The interaction of these molecules with positive growth factors, the role of synergy with other negative regulators, and their role in the pathogenesis of bone marrow failure are discussed. Lymphokine and lymphocyte abnormalities in aplastic anemia may be manifestations of an underlying viral etiology. Three examples are discussed: Epstein-Barr virus-associated aplastic anemia; B19 parvovirus bone marrow failure; and HIV-induced neutropenia.
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PMID:Autoimmune aspects of aplastic anemia. 297 24

To produce concentrations of zidovudine (AZT) in plasma and cerebrospinal fluid that would provide constant inhibition of the replication of human immunodeficiency virus (HIV), we gave AZT by continuous intravenous infusion to 21 children ranging in age from 14 months to 12 years who had acquired HIV infection through transfusions or perinatally. All patients were symptomatic before AZT treatment (Class P2 of the Centers for Disease Control); 13 (62 percent) had evidence of neurodevelopmental abnormalities. The mean CD4/CD8 ratio was 0.18; 11 patients had CD4 counts below 0.2 x 10(9) per liter. We administered AZT at four dose levels: 0.5, 0.9, 1.4, and 1.8 mg per kilogram of body weight per hour. The plasma drug concentrations achieved at the respective dose levels were 1.9 +/- 0.3, 2.8 +/- 1.4, 3.1 +/- 1.1, and 4.5 +/- 1.0 microM. The steady-state cerebrospinal fluid:plasma ratio was 0.24 +/- 0.07. The only evidence of toxicity was bone marrow suppression. Transfusion was required in 14 patients because of low levels of hemoglobin (5 mmol per liter [less than 8 g per deciliter]). Dose-limiting neutropenia (less than 0.5 x 10(9) polymorphonuclear leukocytes per cubic millimeter) occurred in most patients who received doses of 1.4 mg per kilogram per hour or more. Improvement in neurodevelopmental abnormalities occurred in all 13 children who had presented with encephalopathy before treatment. Serial measurements of IQ before therapy and after three and six months of continuous therapy with AZT showed that IQ scores, including those for verbal and performance IQ, rose in these 13 patients and in 5 other children who had no detectable evidence of encephalopathy before treatment. Most patients also had increased appetite and weight, decreased lymphadenopathy and hepatosplenomegaly, decreased immunoglobulin levels, and increased numbers of CD4 cells. In some patients the improvement in the features of encephalopathy occurred despite the absence of immunologic improvement. We conclude that AZT is beneficial in children with symptomatic HIV infection, especially those with encephalopathy (which may be subclinical), and that the optimal continuous intravenous dose of AZT in children is between 0.9 and 1.4 mg per kilogram per hour.
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PMID:Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection. 263 49

A 60-year-old male patient, originating from West Africa, developed acute and regressive neurologic symptoms associated with aphasia, apraxia, acalculia, behavioral impairments, and an epileptic phase. Eighteen months after the onset of the disease, the patient was almost normal. All along the clinical course, biological abnormality patterns were minor. We noted only a mild neutropenia in the blood. We also observed a weak lymphocytosis and elevated protein content in the cerebrospinal fluid. Electroencephalogram examination revealed slow waves which disappeared after remission. A weak ventricular dilatation was detected on CT scan. Neither vascular, nor tumoral, nor a classical infectious origin could be identified. While the patient was seronegative to HIV, a HIV-like virus was isolated twice from his peripheral blood lymphocytes during the disease. Eighteen months later, the patient remained seronegative. He developed neither AIDS nor immunodeficiency. The subtype of HIV has been isolated and characterized, and its neurotropism is being investigated.
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PMID:Isolation of HIV in a seronegative demented patient without symptoms of immune deficiency. 318 Jan 31

Antiviral agents under investigation for the treatment of patients infected with the human immunodeficiency virus (HIV) are reviewed. Multiple mechanisms exist by which antiviral agents might inhibit the replication of HIV or eradicate its latent form in affected cells, or both. These mechanisms include (1) interference with the cell surface receptor for HIV, (2) prevention of uncoating of viral particles, (3) inhibition of reverse transcriptase, (4) prevention of integration and posttranscription processing, (5) interference with viral assembly, and (6) interference with virus release. Most agents developed thus far work by inhibiting HIV reverse transcriptase. Suramin, ribavirin, ammonium 21-tungsten-9-antimoniate (HPA-23), foscarnet (phosphonoformate, PFA), inosine pranobex (isoprinosine), peptide T, ampligen, AL 721, dideoxycytidine, and zidovudine (formerly azidothymidine) have antiretroviral activity in vitro. To date zidovudine is the only antiretroviral agent approved by the FDA as clinically effective. However, zidovudine has serious toxicities, including neutropenia and anemia; in some patients dosage reduction or cessation of therapy may be necessary. Because treatment with zidovudine does not cure HIV infection, numerous studies are under way with other anti-HIV agents. Ultimately, combinations of agents probably will be used to suppress or eradicate HIV. While the search for more efficacious and less toxic treatments continues, the development of zidovudine in such a short time provides hope that progress toward a cure will be made rapidly.
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PMID:Development of antiviral agents for the treatment of human immunodeficiency virus infection. 332 38

The incidence of lymphopenia, thrombocytopenia and neutropenia was studied in 105 homosexual men with HIV infection. Lymphopenia was common in patients with AIDS (75%), but its incidence in PGL (24%) was not significantly different from that in asymptomatic anti-HIV positive (15%) homosexual men. Neutropenia and thrombocytopenia were found in patients with AIDS or PGL, but not in asymptomatic anti-HIV positive homosexuals. The study suggests that the neutropenia and thrombocytopenia in these patients were due to autoimmune destruction of neutrophils and platelets.
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PMID:Incidence and mechanism of neutropenia and thrombocytopenia in patients with human immunodeficiency virus infection. 362 Mar 53

Patients infected with the human immunodeficiency virus (HIV) often present with neutropenia. To elucidate the mechanism(s) of this HIV-related neutropenia, we assessed the proliferative capacity of the granulocyte-macrophage progenitor cell (CFU-GM) from the bone marrow (BM) of 78 patients within the AIDS spectrum manifesting symptoms or signs related to HIV infection. Of these, 70 had a significant deficit in the growth of this committed progenitor when compared with normal controls (P less than .01). Further analysis revealed that the nucleated bone marrow cells from AIDS and AIDS-related complex (ARC) patients inhibited the growth of CFU-GMs from normal individuals when cocultured in agar (P less than .001). Control CFU-GMs were also inhibited when they were cultured over feeder layers containing patients' BM cells (P less than .001). Conditioned media obtained from the liquid culture of patients' BM cells did not inhibit normal control CFU-GM growth to a degree different from that of the cells themselves (P greater than .4). Analysis of these conditioned media by polyacrylamide gel electrophoresis (PAGE) revealed a unique glycoprotein (gp) with a mol wt of 84 kd. Further studies revealed that this gp possessed the inhibitory activity. These data suggest that this gp may be an important factor in HIV-related neutropenia. The presence of gp84 was independent of drugs administered to the patients.
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PMID:A glycoprotein inhibitor of in vitro granulopoiesis associated with AIDS. 366 34


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