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

Several dideoxynucleosides, including 3'-azido-2',3'-dideoxythymidine (zidovudine, azidothymidine, AZT), 2',3'-dideoxycytidine (ddC), and 2',3'-dideoxyinosine (ddI), have been shown to be potent inhibitors of human immunodeficiency virus (HIV) replication in human T cells and macrophages. These compounds undergo anabolic phosphorylation within target cells to a 3'-triphosphate moiety; as triphosphates, they act at the level of HIV DNA polymerase (reverse transcriptase). AZT has been shown to reduce the morbidity and mortality of patients with severe HIV infection and to at least temporarily ameliorate certain cases of HIV-induced dementia. In phase 1 studies, ddC and ddI have been shown to induce immunologic and virologic improvements in patients with AIDS or related disorders; phase 2 studies of ddC and ddI are underway. The use of these drugs can be associated with toxicity. AZT can cause bone marrow toxicity or myositis with prolonged use, ddC can cause peripheral neuropathy at high doses, and ddI can cause sporadic pancreatitis and peripheral neuropathy at high doses. For each compound, however, a therapeutic window exists in which an anti-HIV effect can be attained without short-term toxicity in most patients. Dose-intensity appears to be an important determinant of the toxicity of dideoxynucleosides. Studies are underway to explore how the therapeutic profiles of these compounds may be enhanced by attention to scheduling or through the use of combination therapy.
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PMID:Initial clinical experience with dideoxynucleosides as single agents and in combination therapy. 207 27

The dideoxynucleosides 3'-azido-3'-deoxythymidine (zidovudine, AZT) and 2',3'-dideoxycytidine (ddC) are potent inhibitors of human immunodeficiency virus (HIV) in vitro and improve surrogate measures of HIV infection in vivo. Long-term administration of AZT has been associated with significant hematologic toxicity and has resulted in virus with reduced in vitro susceptibility. Although ddC does not have significant hematologic toxicity and has not shown cross-resistance with AZT in vitro, ddC has been associated with a severe dose-related peripheral neuropathy. Given the independent activity of each agent, their non-overlapping toxicity profiles, and the absence of cross-resistance, it was hypothesized that concurrent administration of AZT and ddC in low doses might be at least as active as either drug given individually at higher doses in the treatment of HIV infection. It was further hypothesized that combined low doses of both drugs would reduce the incidence of serious side effects and the development of resistance. A phase I/II dose-finding trial of six different regimens of combination AZT and ddC in persons with acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex was initiated to test these hypotheses.
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PMID:AIDS Clinical Trials Group: phase I/II study of combination 2',3'-dideoxycytidine and zidovudine in patients with acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex. 215 7

Four cases of plasma cell type Castleman's disease (CD) are described. Two patients had localized forms (one mediastinal and the other mesenteric) and presented systemic manifestations associated with hypergammaglobulinemia and severe anemia. In both cases, the lesions were revealed by computerized tomography scans and cures were obtained by the complete surgical removal of the masses, which led to the rapid disappearance of the systemic manifestations. The other 2 patients had the multicentric form of CD and presented more extensive clinical and biological symptoms. One of these developed severe peripheral neuropathy and endocrine anomalies during the late phase of his disease, which led us to discuss the relationship between multicentric CD and the POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin change) syndrome first described in Japan. Three of our patients presented with hypochromic microcytic anemia too severe to be explained by an inflammatory syndrome alone, and was likely due to several mechanisms. The etiology of CD remains unknown. The histological characteristics of angiofollicular lymph node hyperplasia are among the most important criteria for the diagnosis of localized and multicentric forms of CD, which can easily be made on a lymph node biopsy. However, it must be noted that this lesion can also be observed (but only rarely) in HIV (human immunodeficiency virus) - infected patients. The localized form is always considered to be benign, but, to date, there is no formal argument definitively supporting the malignancy of the multicentric one, in spite of its clinical similarity to a lymphoproliferative syndrome.
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PMID:[Castleman's disease (giant lymph node hyperplasia): clinical, biological and developing polymorphism. Apropos of 4 cases]. 216 41

Ninety-two adult patients with AIDS or severe AIDS-related complex were treated with 2',3'-dideoxyinosine (didanosine; ddI) at dosages ranging from 0.8 to 66.0 mg/(kg.d) for at least 6 weeks in phase I trials. Potentially beneficial changes in weight (40% of patients), clinical signs or symptoms (40% of patients), CD4+ cell counts (25% of patients), and serum levels of HIV p24 antigen (50% of antigen-positive patients) were reported. Response rates tended to be higher among patients with AIDS-related complex and among those who had not received prior zidovudine therapy. A major response (improvement in at least one clinical parameter and in at least one laboratory marker) occurred in 29% of patients, and rates of major response tended to be higher in patients receiving higher dosages. The primary dose-limiting toxicity observed was peripheral neuropathy, which was observed with increasing frequency in patients receiving greater than 20 mg/(kg.d). Of the other adverse effects, pancreatitis was possibly dose-dependent and hyperuricemia (without clinical gout) occurred only at high doses. Dosages of 250 mg and 375 mg of ddI twice daily will be used in extended phase II/III studies.
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PMID:Overview of phase I trials of 2',3'-dideoxyinosine (ddI) conducted on adult patients. 216 65

The AIDS dementia complex and peripheral neuropathy in AIDS are considered to be direct or indirect manifestations of HIV infection, yet the pathogenesis in unclear. There are parallels between AIDS and Tangier disease clinically and histopathologically and in lipid metabolism. The neurological disorders in AIDS may be caused by dysfunction of cellular cholesterol transport. Substitution of high density lipoprotein is recommended in the treatment of severe polyneuropathy and dementia in AIDS.
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PMID:Abnormalities in cholesterol metabolism cause peripheral neuropathy and dementia in AIDS--a hypothesis. 217 10

At least 60% of patients infected with the human immunodeficiency virus (HIV) develop neurologic disorders. These may be the direct result of human immunodeficiency virus (HIV) infection, opportunistic infections, neoplastic disorders, or cerebrovascular complications. Neurologic diseases associated with HIV infection include encephalopathy, aseptic meningitis, vacuolar myelopathy, peripheral neuropathy, and myopathy. The pathogenesis of these diseases is not known, but it is likely that they will differ. There is evidence that HIV is the etiologic agent of HIV-associated meningitis and subacute encephalitis, but to date there is little evidence to implicate HIV directly as the cause of vacuolar myelopathy, peripheral neuropathies, and myopathies. The results of preliminary clinical studies suggest that treatment with zidovudine (Retrovir) may cause improvement in some patients.
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PMID:Neurologic disorders associated with HIV infections. 219 51

Bilateral radial nerve palsies are rare, and hence in this situation an underlying generalized peripheral neuropathy must always be considered. Among 103 patients with radial nerve palsies seen at our department during the last five years, there were three cases presenting with bilateral non-traumatic radial nerve palsies. These patients are presented in detail. One had a bilateral nerve entrapment in the supinator channel associated with a neuropathy of unclear origin, the second had bilateral sleep palsy, and the third had mononeuropathy multiplex associated with HIV infection. Following a summary of the cases reported in the literature, diagnostic considerations and additional investigations are discussed.
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PMID:[Bilateral radial nerve paralysis. Diagnostic and differential diagnostic aspects]. 221 54

The majority of drug users neglect their health and have limited access to primary and preventative health care services. A health care team was developed in an attempt to provide health care for drug users, to prevent the spread of HIV and provide health education to the drug users. The health problems were related to injecting drugs, comprising abscesses, peripheral neuropathy and poor peripheral circulation. A high level of past infection with hepatitis B virus was noted, indicating the need for hepatitis B vaccination for drug users.
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PMID:The practical business of treatment--13. Providing health care for drug users? 228 56

Oropharyngeal candidiasis occurred in a previously healthy young Israeli homosexual male. Additional symptoms included persistent diarrhea, weight loss, fever, generalized lymphadenopathy and peripheral neuropathy. Immunologic studies revealed lymphopenia with reversed T-helper/T-suppressor cells ratio and antibodies to human immunodeficiency virus, all compatible with the diagnosis of subclinical AIDS. Repeated courses of antimonilial treatment failed to eradicate the oropharyngeal lesions. The clinical picture of AIDS, particularly its oral manifestations, is described. The diagnostic and prognostic implications of oropharyngeal candidiasis as a presenting sign of the disease are discussed. In addition, precautionary measures that should be taken when treating persons infected with HIV are described.
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PMID:AIDS and oropharyngeal candidiasis. 249 Sep 31

Nerve and muscle biopsies were performed on 20 patients with HIV infection and peripheral neuropathy. Nine patients had distal symmetrical peripheral neuropathy (DSPN) (six ARC and three AIDS), six had inflammatory demyelinating polyneuropathy (IDP) (three ARC, one AIDS, and two otherwise asymptomatic patients), one had mononeuropathy multiplex (MM) (AIDS), 1 had mononeuropathy (ARC), one had meningoradiculitis (AIDS), and two had areflexia-associated lymphocytic meningitides (ARC), DSPN exhibited axonal degeneration in four of nine cases and was associated with segmental demyelination in five of nine cases. IDP exhibited segmental demyelination associated with axonal degeneration in four of six cases. Demyelination was more frequent in asymptomatic patients (2 of 2 cases) and in ARC (7 of 12 cases), whereas axonal degeneration was predominant in AIDS (6 of 6 cases). Mononuclear cell infiltration was seen in 1 of 2 asymptomatic patients and in 11 of 12 ARC patients but was exceptionally found in AIDS (1 of 6 cases). Involvement of the walls of small vessels, mostly venules ("subacute microvasculitis"), was found in 1 of 2 asymptomatic patients, in 8 of 12 ARC patients, and never in AIDS. The polyclonal mononuclear cell population was composed mainly of Leu 2 (T8) positive cells in seven cases of ARC. No virions were seen in electron microscopy. HIV was isolated in two cases from the CSF or the nerve biopsy.
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PMID:The spectrum of changes on 20 nerve biopsies in patients with HIV infection. 254 87


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