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

Advances in the development of antiviral drugs have been rapid and dramatic. Since the recognition of HIV-1 as the cause of AIDS in 1984, and improved understanding of retroviral replication and pathogenesis, three antiviral drugs, Zidovudine, Didanosine, and Zalcitabine, have been developed to the point of routine use in humans. There is substantial experience with the former two in children. Despite being unable to cure HIV-1 infection, the benefits of antiretroviral therapy, including extended survival and reductions in opportunistic infections in adults, and improved weight gain and well-being in children, are strong arguments for routine treatment of symptomatic disease. Because these agents may also interfere with human cellular processes and have toxicities including anemia, neutropenia, pancreatitis, and neuropathy, their routine use for the treatment of asymptomatic children requires further controlled study. There are multiple candidate agents being developed for entry into clinical trials. An additional potentially effective strategy is the use of combinations of drugs at the same time or in sequence to maximize the viral targets being attacked, while minimizing toxicity, and to prevent the emergence of a drug-resistant virus.
 ...
PMID:Antiretroviral therapy for children. 783 65

To determine the effect of zidovudine (ZDV) on the pharmacokinetic disposition of recombinant soluble CD4 immunoglobulin G (rCD4-IgG) and to evaluate the safety and preliminary activity of concurrent administration of ZDV with rCD4-IgG, we undertook an open-label, dose-escalating, 12-week study. The regimens of intravenous rCD4-IgG and oral ZDV we used were (a) 300 micrograms/kg rCD4-IgG twice per week and 300 mg ZDV per day, (b) 300 micrograms/kg rCD4-IgG twice per week and 600 mg ZDV per day, (c) 1,000 micrograms/kg rCD4-IgG twice per week and 300 mg ZDV per day, (d) 1,000 micrograms/kg rCD4-IgG twice per week and 600 mg ZDV per day, and (e) 3,000 micrograms/kg rCD4-IgG twice per week and 300 mg ZDV per day. Subjects were recruited from three AIDS clinical trials units. Forty-one patients with HIV infection who had CD4 cell counts < or = 500 cells/mm3 and < 120 days of previous ZDV therapy participated. Pharmacokinetic interactions were assessed with the second regimen. Mean calculated peak serum rCD4-IgG concentrations were 5.47 micrograms/ml with ZDV and 8.28 micrograms/ml without ZDV, with serum half-lives of 34.2 and 32.0 h, respectively. Antibodies to rCD4-IgG were not detected. Seven episodes of severe adverse events occurred in five patients: one episode each of severe nausea, fever, or abnormal liver function tests and four episodes of severe neutropenia. Mean hemoglobin and neutrophil counts decreased, and mean platelet counts increased in all regimens, but there were no significant differences among regimens, rCD4-IgG dose, or ZDV dose.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Combination therapy with recombinant human soluble CD4-immunoglobulin G and zidovudine in patients with HIV infection: a phase I study. 783 98

Pyomyositis is an infection of the skeletal muscle mostly caused by Staphylococcus aureus. Patients in Western countries affected by pyomyositis associated with AIDS tend to be neutropenic. The objective of this study was to find out whether neutropenia is a common feature of African AIDS patients with pyomyositis; therefore, an African sample was compared with a sample of Western patients obtained from the international literature. During January-December 1993, 30 patients with pyomyositis were admitted to the Surgical Ward of Dr. Ambrosoli Memorial Hospital in Kalongo, Uganda. 11 (36.6%) were found positive for HIV and were in stage IV of the disease. The mean age was 28 years, 3 were females and 8 were males. The neutrophil count was performed before the surgical evacuation of muscle abscess. In the international literature, eight reports of 17 patients with AIDS and pyomyositis were located during the period of 1988-92. All were males in stage IV with a mean age of 37.3 years; 8 were treated with zidovudine. When the neutrophil count was below 3000/cu. mm, the patient was considered neutropenic. 12 out of 17 Western patients were neutropenic, as opposed to only 1 out of 11 Ugandan patients (p 0.01). The mean neutrophil count of Western patients was 3547; that of Ugandan patients was 9077 (p 0.01). Neutrophils are primary effector cells in host defense against staphylococcal infections such as pyomyositis; hence, it has been suggested that neutropenia contributes to the development of pyomyositis in AIDS patients. Neutrophils from AIDS patients were demonstrated to be defective in their ability to kill Staphylococcus aureus in vitro, compared with neutrophils from seronegative controls. Therefore, the defective neutrophil function associated with HIV infection contributed to the development of pyomyositis in Ugandan patients, among whom neutropenia was not common.
 ...
PMID:Absence of neutropenia in African patients with AIDS and associated pyomyositis. 785 59

In this double-blind, placebo-controlled trial of HIV-infected asymptomatic haemophiliacs, the efficacy of 2-year zidovudine therapy (1000 mg daily in two divided doses) in preventing progress of HIV infection was prospectively evaluated. Drug tolerance was also studied. 143 haemophiliacs from five European countries and Australia with p24 antigenaemia and/or CD4 cell counts of 0.1-0.4 x 10(9)/l were enrolled. The main measures of outcome were progression to AIDS, CDC group IV disease, symptomatic HIV-related disease, and a decrease in CD4+ T-lymphocyte count to fewer than 0.2 x 10(9)/l. There were no significant treatment differences in the proportion of patients progressing to AIDS, CDC group IV or symptomatic disease. Analysis of time to CD4+ counts less than 0.2 x 10(9)/l showed a non-significant trend in favour of zidovudine. Haemoglobin concentrations were less than 8 g/dl in 4% of zidovudine recipients; neutropenia was less than 0.75 x 10(9) cells/l in 5% of zidovudine recipients; alanine aminotransferase levels were greater than 10 times the upper normal limit in 3% of zidovudine recipients, but also in 4% of placebo recipients. Hence there was a very low prevalence of side-effects in haemophiliacs, despite the use of a higher zidovudine dosage than is currently widely used.
 ...
PMID:Randomized double-blind, placebo-controlled trial of twice-daily zidovudine in asymptomatic haemophiliacs infected with the human immunodeficiency virus type 1. European-Australian Haemophilia Collaborative Study Group. 791 97

HIV-infected patients commonly experience haematological disturbances including anemia, neutropenia or thrombocytopenia. Bone marrow failure may be caused by HIV itself, or by secondary involvement by opportunistic pathogens and malignancy. The need for multiple concomitant suppressive treatments may increase the risk of cytopenias. Strategy to reduce both anemia and neutropenia as well as to improve the haematological tolerance to myelotoxic agents have been developed by using haematological growth factors. So far, erythropoietin and granulocyte(macrophage) colony-stimulating factors have been successfully used in clinical trials including HIV-patients with either zidovudine-associated anemia or severe HIV or drug-induced neutropenia. However, according to the cost of these palliative approaches, there is a need for more reliable data showing that these growth factors could really have a major impact on the patient's compliance to therapy, reduction of hospitalization and infection rate and improvement of the overall survival.
 ...
PMID:Clinical use of haematological growth factors in patients with human immunodeficiency virus (HIV-1) infection. 791 7

Neutropenia induced by antiviral treatment, in particular AZT, can be improved with recombinant human granulocyte macrophage colony stimulating factor (RHGMCSF) in HIV positive patients. However, there has been concern that this may increase the HIV load in the mononuclear cells of such patients. Five patients receiving AZT plus low dose RHGMCSF are reported. There was no consistent change in the levels of HIV DNA in the monocytes and lymphocytes. Additionally, all patients had stable disease with no opportunistic infection during the study period. It is concluded, therefore, that low dose RHGMCSF does not significantly change the viral DNA load in patients receiving AZT.
 ...
PMID:Quantification of HIV by PCR in monocytes and lymphocytes in patients receiving antiviral treatment and low dose recombinant human granulocyte macrophage colony stimulating factor. 796 59

The efficacy of KRN8601 for neutropenia associated with HIV infection was evaluated in 24 patients. KRN8601 was infused intravenously at a dosage of 200 micrograms/m2 for 14 consecutive days. Neutrophil counts recovered in 19 (90.5%) out of 21 evaluable patients by KRN8601 treatment. The concomitant myelosuppressive agents for the treatment of HIV infection and complications could be continued without dose reduction in 15 (88.2%) out of 17 patients. The clinical improvement was observed in 66.7% (12/18) of patients who were treated with anti-microbial agents for opportunistic infections which indicates that KRN8601 shows an additive effect on infections when it was given with anti-microbial agents. Adverse events and abnormal laboratory findings were observed in 3 and 7 patients, respectively, and they were reversible and tolerable. This study demonstrated that KRN8601 improved neutropenia with HIV infection, made possible to continue the full dose of myelosuppressive treatments and have additive effect on the treatment of secondary infections.
 ...
PMID:[Phase III clinical trial of KRN8601 (rhG-CSF) for neutropenia in patients with human immunodeficiency virus infection]. 796

Valaciclovir, the L-valyl ester of acyclovir, is rapidly and extensively converted in humans to acyclovir after oral administration by first-pass metabolism. A phase I study was conducted in two cohorts of volunteers with advanced human immunodeficiency virus (HIV) disease (absolute CD4 lymphocyte count of < 150 cells per microliters) who received oral valaciclovir at dosages of 1,000 or 2,000 mg four times daily for 30 days. All patients were clinically stable without any changes in underlying HIV-related medications for > or = 6 weeks prior to entry in study; these medications were continued throughout the study. Multiple-dose administration of valaciclovir showed a generally favorable safety profile. Nausea, vomiting, diarrhea, and abdominal pain each were reported in < or = 31% of the patients; of these symptoms, only one episode of diarrhea was considered causally related to valaciclovir exposure. Four patients developed neutropenia (two at each dose level) which was not clinically significant. There were no renal or neurologic adverse events. Valaciclovir was rapidly absorbed and converted to acyclovir, with plasma valaciclovir levels generally undetectable or levels of < or = 0.4 microgram/ml. After 3 h postdosing, valaciclovir was not detectable in plasma. Acyclovir was measurable in plasma as early as 15 min following valaciclovir dosing, and plasma concentrations of acyclovir greatly exceeded those of valaciclovir. The mean values for the maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, area under the concentration-time curve from 0 h to infinity, and apparent half-life of acyclovir obtained after single- and multiple-dose valaciclovir administration in HIV-infected patients were similar to those reported in normal healthy volunteers. The time to maximum concentration in serum and half-life of acyclovir after valaciclovir administration were approximately 2 and 3 h, respectively, which were similar to those reported after oral administration of acyclovir itself. The mean trough and peak acyclovir concentrations and the daily area under the concentration-time curve acyclovir values at steady state were 2.5 and 8.4 micrograms/ml and 120 h micrograms/ml, respectively, after a dosage of 2,000 mg of valaciclovir four times daily. These values were approximately fivefold greater than those achieved with high dosages of oral acyclovir (800 mg, five times daily) and were not affected by continued use of medications necessary for management of advanced HIV disease. Thus, 2,000 mg of valaciclovir given orally four times daily should be evaluated for its potential efficacy in suppressing cytomegalovirus and other herpes group virus infections not optimally managed with current oral acyclovir therapy.
 ...
PMID:Phase I trial of valaciclovir, the L-valyl ester of acyclovir, in patients with advanced human immunodeficiency virus disease. 797 85

The severe immunosuppression associated with HIV infection increases susceptibility to opportunistic fungi. We describe a primary gangrenous cutaneous infection caused by Rhizopus arrhizus in an HIV-infected intravenous narcotic user. In addition, we review nine reported cases of zygomycosis in HIV-infected patients and discuss the frequency and outcome of zygomycosis in HIV infection. Eight of 10 patients were intravenous drug users. Cutaneous infection occurred in four patients. Another case was associated with drug-induced neutropenia. With treatment, 60% of the patients recovered. HIV-induced immunosuppression rarely predisposes to zygomycosis except in intravenous drug users or persons with other risk factors for this fungal infection.
 ...
PMID:Zygomycosis and HIV infection. 816 72

Pseudomonas aeruginosa infection is unusual in individuals with human immunodeficiency virus infection, and it most often occurs in the setting of other risk factors, such as neutropenia or cytotoxic drug use. We noted an increasing number of pulmonary isolates of this organism in our clinic population and sought to describe the clinical correlates of this finding. Our study consisted of a retrospective review of the microbiology, radiology, and clinical records of 1,852 HIV-seropositive adults seen at a university-based outpatient AIDS clinic. We identified 16 individuals with Pseudomonas bronchopulmonary infection. All subjects had advanced HIV disease with prior AIDS diagnoses, and mean CD4 counts of 25/mm3 (0.025 x 10(9)/L). Pseudomonas was the sole pulmonary pathogen in 14 of 16 patients and was associated with new chest X-ray abnormalities in 14 cases. Four individuals had acute pseudomonal pneumonia with sepsis; this presentation was associated with hospitalization and other known risk factors for Pseudomonas infection. In contrast, 12 patients had more indolent, community-acquired infection, which had a low mortality rate and occurred in the absence of other risk factors. Survivors of the initial bout of Pseudomonas infection had an 86% relapse rate despite a median survival of only 4.5 months. This pattern of pseudomonal disease is reminiscent of cystic fibrosis and suggests a role for maintenance therapy.
 ...
PMID:Pseudomonas aeruginosa bronchopulmonary infection in late human immunodeficiency virus disease. 821 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>