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)

In this paper we describe the current status of the chemotherapy of HIV-related disease, and the newly emerging approaches to this problem. Azidothymidine, the first anti-HIV drug, is now used by thousands of patients with AIDS, and is able to induce a substantial improvement of their clinical status. However, due to its toxicity and its very limited activity against HIV replication in chronically infected cells (the natural reservoir of the virus in the body), it is crucial that new drugs be developed. A number of compounds belonging to the dideoxynucleoside family (the same of AZT) have been synthesized and used in HIV-infected patients, with promising results. Nevertheless, new compounds with different mechanisms of action, and with excellent anti-HIV efficacy need to be developed, particularly those that can inhibit the late stages of HIV replication. This will permit a polychemotherapeutic approach against HIV infection that, as in the case of anticancer chemotherapy, has conceivably better chances to be effective in patients with HIV-related disease.
 ...
PMID:[New therapeutic trends in AIDS]. 131 26

Lymphocytes infected in vivo with HIV or lymphoblastoid cells exposed in vitro to either HIV or its envelope glycoprotein (gp120) show a defect in inositol polyphosphate-mediated signal transduction together with an associated abnormality in intracellular calcium regulation. The defect in patients reverses after treatment with the anti-retroviral agent zidovudine (AZT). We present evidence that the defect is at the level of the Ins (1,3,4,5)P4 5-phosphomonoesterase (PME) in these cells and that, though elevation of the intracellular ATP level partially down-regulates the activity of this enzyme, such changes alone are unable to account for the complete inhibition seen in HIV-infected cells.
 ...
PMID:The defect seen in the phosphatidylinositol hydrolysis pathway in HIV-infected lymphocytes and lymphoblastoid cells is due to inhibition of the inositol 1,4,5-trisphosphate 1,3,4,5-tetrakisphosphate 5-phosphomonoesterase. 132 Oct 14

HIV-related chronic ITP is caused by an accelerated platelet destruction due to adsorption of circulating immune complexes and to specific anti-platelet antibodies, but perhaps also by a defective thrombopoiesis resulting from invasion of the megakaryocytes by the retrovirus. Treatment is needed when platelet numbers drop beneath 20.10(9)/L or when severe bleeding symptoms occur. Steroids, commercially available immunoglobulins for IV use, AZT and anti-Rh immunoglobulins can be administered, although relapses are frequent after withdrawal of the drugs. Recurrences after splenectomy are far less common, but the progression towards AIDS might be accelerated.
 ...
PMID:HIV-related thrombocytopenia. 132 36

Monocyte/macrophages (M/M) are important targets for HIV in the body, and represent the majority of cells infected by the virus in some body compartments such as the central nervous system (CNS). M/M can be different from T-lymphocytes in terms of surface antigens, cell replication and drug metabolism. Thus, we evaluated, in M/M and in T-lymphocytes, the pattern of viral inhibition induced by various anti-HIV drugs, and assessed some of the mechanisms of action related to such antiviral activity. Inhibitors of HIV binding on CD4 receptors have similar activity in M/M and T-lymphocytes, while AZT and other dideoxynucleosides (ddN) are in general more active against HIV in M/M than in T-lymphocytes. This phenomenon can be related to the increased ratio in M/M of ddN-triphosphate/deoxynucleoside-triphosphate, and can at least in part explain the ability of zidovudine and didanosine in improving neurological dysfunctions in AIDS patients. Moreover, the antiviral activity of AZT (but not of other ddN- or HIV-binding inhibitors) is potently enhanced by cytokines like granulocyte-macrophage colony stimulating factor (GM-CSF) in M/M, while anti-HIV activity of TIBO compounds in M/M is not down-modulated by GM-CSF and other cytokines. Finally, non-toxic concentrations of adriamycin, an anticancer drug reported to be active against DNA viruses, can inhibit HIV replication in M/M (but not in T-lymphocytes). Taken together, these results suggest that M/M are selective targets for HIV with peculiarities different from those of T-lymphocytes. Thus, promising anti-HIV compounds should be evaluated both in T-cells and in M/M before reaching clinical trials. This may help in selecting drugs with good chances of being effective in patients with HIV-related disease.
 ...
PMID:Different pattern of activity of inhibitors of the human immunodeficiency virus in lymphocytes and monocyte/macrophages. 132 45

Combination antiretroviral therapy is an important development in the management of HIV infection. AZT with ddC is the first such combination to be approved for clinical use. Several issues remain, however, including the precise clinical benefit and toxicity of combination therapy, its effect on drug resistance, and the development of ever more effective therapeutic strategies.
 ...
PMID:Treatment of HIV infection: the antiretroviral nucleoside analogues. Nucleoside analogues: combination therapy. 132 54

At present, the nucleoside analogues are the cornerstone of therapy for HIV infection. Of the three that have been approved for clinical use, AZT is the only one that has clearly proved to prolong survival. ddI is indicated for patients who develop toxicity or resistance to AZT. Current data do not support ddC monotherapy as first-line treatment.
 ...
PMID:Treatment of HIV infection: the antiretroviral nucleoside analogues. Nucleoside analogues: monotherapy. 132 57

The combination of zidovudine (AZT) and 2',3'-dideoxycytidine synergistically inhibits human immunodeficiency virus type 1 (HIV-1) replication in vitro with AZT-sensitive and AZT-resistant clinical isolates and HIV-1IIIB. Synergy was determined by the median-effect principle and isobologram techniques. Cytotoxicity of the agents was not observed. Clinical trials are ongoing to define the combination's role in HIV-1 therapy.
 ...
PMID:Synergistic inhibition of replication of human immunodeficiency virus type 1, including that of a zidovudine-resistant isolate, by zidovudine and 2',3'-dideoxycytidine in vitro. 132 48

HIV-1-related neurological diseases, excluding opportunistic infections and HIV encephalitis, are considered here. Most occur in severely immunosuppressed patients, with CD4 counts of under 200 x 10(6) l-1. Primary brain lymphoma and metastases from systemic non-Hodgkin's lymphoma, the second commonest cause of cerebral mass lesions in AIDS, are usually aggressive B cell tumours. Their poor median survival after treatment, compared with that of lymphomas in non-AIDS patients, seems related to systemic complications, particularly opportunistic infections. Kaposi's sarcoma produces neurological symptoms exceptionally. Cerebral infarction is often unrecognized clinically but large vessel arteritic occlusions may occur. Intracranial haemorrhages occur mostly in thrombocytopenic patients. Seizures are frequently referred to the neurologist; investigation may lead to a diagnosis of AIDS. Nearly 50% of patients with seizures have cerebral toxoplasmosis or cryptococcal meningitis; HIV-1 encephalitis is presumed to be the cause in 30%. A subacute or chronic vacuolar myelopathy with pyramidal and posterior column signs is the commonest form of spinal cord involvement in AIDS; its cause remains unknown. Peripheral nerve syndromes occur at all stages of HIV-1 infection. Distal symmetrical peripheral neuropathies are the most frequent, particularly a painful form with axonal atrophy, associated with CMV infection, and seen during ARC or AIDS. Mononeuritis multiplex due to vasculitis, CMV, or lymphoma and a serious lumbosacral polyradiculopathy due to CMV are infrequent. The commonest myopathy is due to zidovudine (AZT); it usually responds to drug withdrawal. The nature, prognosis and optimal management of most other myopathies is yet to be determined.
 ...
PMID:Other neurological diseases in HIV-1 infection: clinical aspects. 134 49

Retroviruses of the nervous system cause HTLV-1-associated myelopathy and HIV-associated diseases. The treatment of HTLV-1 disease is essentially conservative; there is no effective drug treatment and therefore patients should be simply supported and reassured. If appropriate, other members of the family should be tested for HTLV-1 disease and counselled. The effects of HIV on the nervous system are much more complex. Therapy must take account of the diverse complications of HIV disease. Patients are probably best managed in specialized clinics which can cope with the different manifestations of the disease. Zidovudine (AZT) is the only effective anti-HIV drug that is licensed. It is indicated in complicated seroconversion disease and for any manifestation of HIV progression including AIDS dementia complex. Management of severe neurological disease depends critically on the ability to diagnose and treat CNS-specific opportunistic infections. Whether zidovudine is indicated for early asymptomatic disease when CD4 counts are below 500 microliters-1 is controversial. The main problems of zidovudine are reversible anaemia which results in about 30% of patients not tolerating long-term use, and the development of drug resistance which may be associated with clinical failure of the drug. Other, new and experimental drug treatments are discussed but none of them has as yet shown any convincing evidence of efficacy. Future improvements in treatment appear to depend on the development of effective multiple drug regimens (concurrently or sequentially) which will overcome the challenge of drug resistance.
 ...
PMID:Therapeutic aspects of retroviral disease. 134 52

Compounds with medium relative molecular masses active against human immunodeficiency virus (HIV) were synthesized. Sulfated alkyl oligosaccharides such as sulfated octadecyl maltohexaoside, sulfated dodecyl laminaripentaoside and sulfated dodecyl laminari-oligomer caused 50% inhibition of virus infection in the EC50 range of 0.4-0.7 microgram/mL in vitro using the MT-4 cell line and HIV-1HTLV-IIIB virus isolate, though sulfated oligosaccharides without alkyl groups showed low anti-HIV activities. This anti-HIV activity was close to the EC50 of 0.43 microgram/mL for a highly active sulfated polysaccharide curdlan sulfate which was reported to inhibit completely the HIV infection at a concentration as low as 3.3 micrograms/mL. These compounds were also active against HIV-2 and a clinically isolated HIV-1 with reduced AZT sensitivity. For such sulfated alkyl oligosaccharides, the mechanism of inhibition of HIV infection was assumed to be the inhibition of HIV binding to the cell and to some extent the interaction of the alkyl portion with the lipid bilayer of the virus.
 ...
PMID:Sulfated alkyl oligosaccharides with potent inhibitory effects on human immunodeficiency virus infection. 135 27


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