Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of inosine pranobex (Isoprinosine) [corrected] in the treatment of patients with human immunodeficiency virus (HIV) infection but without manifest acquired immunodeficiency syndrome (AIDS). A total of 866 patients were enrolled in 21 centers in Denmark and Sweden. The patients were stratified in three groups according to their CD4+ cell count and randomly assigned to receive either inosine pranobex (1 g three times a day) (n = 429) or matching placebo (n = 437) for 24 weeks. Of the 831 patients who could be evaluated, AIDS developed in 17 in the placebo group as compared with 2 in the inosine pranobex group (P less than 0.001; odds ratio, 8.6 [95 percent confidence limits, 2.2 and 52.6]). There were no significant differences between the groups with respect to changes in CD4+ cell count or the development of other HIV-related conditions, with the exception of thrush, which developed in fewer patients in the inosine pranobex group (P = 0.05). No serious side effects were observed. We conclude that treatment with inosine pranobex delays progression to AIDS in patients with HIV infection. The duration of this beneficial effect, the optimal dose, and the mode of action of inosine pranobex remain to be clarified.
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PMID:The efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. The Scandinavian Isoprinosine Study Group. 170 81

Inosine pranobex (InPx) could prove a valuable and innovative approach to the treatment of HIV-infected patients, since InPx administration has been shown in two multicenter trials to effectively delay the progression of HIV infection to overt AIDS. However, further studies are strongly required to optimize both the dosage of inosine pranobex and the administration schedules. Furthermore, clinical trials evaluating combination therapy of HIV infection with both InPx and zidovudine should ultimately provide an important advance in the management of HIV-infected patients. Our finding that concomitantly administered InPx to zidovudine-receiving patients increased the plasma levels of zidovudine as well as prolonged zidovudine mean half-life during InPx treatment suggests several potential advantages of the combination treatment with both InPx and zidovudine, such as a need for lower zidovudine dosage and a longer interval period between administering zidovudine to obtain sustained plasma levels as well as a potential to enhance residue immune function resulting from inosine pranobex treatment.
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PMID:Inosine pranobex in the treatment of HIV infection: a review. 172 83

Isoprinosine and Imuthiol are immunomodulators with a unique effect on T-cells. The possibility of using them in treating patients with acquired immunodeficiency syndrome related complex (ARC) was initially examined regarding their in vitro effects on peripheral blood mononuclear cells. In six ARC patients Isoprinosine (100 micrograms/ml) and Imuthiol (10 pg/ml) induced in vitro an early chromatin activation as measured by nuclear refringency test and potentiated phytohemagglutinin (5 micrograms/ml) in the same 20-min assay in the absence of fetal calf serum. In all patients an early phytohemagglutinin induced chromatin dispersion was observed with a dose related response before interleukin 2 production can occur. Isoprinosine and Imuthiol increased significantly both the percentage and the absolute number of T4+ cells when peripheral blood mononuclear cells were incubated for 4 days in RPMI supplemented with 10% fetal calf serum. No changes in T8+ cells were noted. Three homosexual ARC patients were then treated p.o. with Imuthiol (5-10 mg/kg/week) for 4 to 6 months. Without any deleterious effect a clinical improvement (in terms of adenopathy and opportunistic infection regression) and restoration of the response to recall antigens were observed in all three patients. One patient with less than 500 T4+ lymphocytes/mm3 exhibited a complete restoration of OKT profiles. In such patients clinical and immunological effects of Isoprinosine have already been reported by others. Altogether these preliminary results indicate that more data should be obtained on the effects of these two agents in ARC patients.
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PMID:Isoprinosine and Imuthiol, two potentially active compounds in patients with AIDS-related complex symptoms. 241 Jan 11

Peripheral blood leukocytes from ARC and AIDS patients were analyzed following phytohemagglutinin- and pokeweed mitogen-induced lymphocyte transformation by dual-color flow cytometry using monoclonal antibodies that identify developmental (HLA-DR) and functional (Leu8) subsets of T cells and monocytes. Significant decreases in both the suppressor regulating helper T subset (Leu3+ Leu8+) and the reciprocal inducer helper T subset (Leu3+ Leu8-) responsible for inducing differentiation of B cells were observed. Simultaneously, the percentages of the effector suppressor T cells and the precursor suppressor T cells were increased, both of which were required for generation of suppression of cell-mediated immunity. There was also a progressive selection of Ia+ cells bearing the Leu2 (Ts) markers and a concurrent reduction of the percentage of antigen-presenting monocytes and activated helper T cells. These results suggest that the functional deficiencies in AIDS may be caused by defects in T-cell activation as well as antigen presentation by monocytes. Isoprinosine induced an increase in both regulator Th (Leu3+ Leu8+) and inducer Th (Leu3+ Leu8+) subsets of helper T cells while potentiating the expression of Ia antigen on helper T cells and monocytes during mitogen-driven DNA synthesis. These events initiated a cascade of cellular interactions leading to partial restoration of cell-mediated immune responses. These interferences with the defective helper/suppressor regulatory pathways may have important therapeutic implications.
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PMID:Isoprinosine-induced modulation of T-helper-cell subsets and antigen-presenting monocytes (Leu M3 + Ia +) resulted in improvement of T- and B-lymphocyte functions, in vitro in ARC and AIDS patients. 244 74

The immunopharmacologic effects of Isoprinosine (INPX) have been associated with clinical benefit to the patient in a number of conditions characterized by immunodeficiency of diverse etiology. Immunodepressed homosexuals at risk of developing acquired immunodeficiency syndrome (AIDS) treated with placebo or INPX experienced an increase in the function and number of immunocompetent cells associated with clinical improvement. A multicenter trial designed to confirm these results has demonstrated that INPX produced an increase in natural killer (NK)-cell activity, total T cells, and T-helper cells, with certain effects persisting for months after completion of the 28-day treatment period. INPX-treated patients also experienced clinical improvement and decreased incidence of progression to AIDS. The administration of INPX for longer periods to patients with frank AIDS under a compassionate-use protocol has also proved useful. Clinical benefit associated with INPX treatment has been demonstrated in other patients with a depressed immune response, such as aged patients, cancer patients, severely burned patients, ill patients, and surgery patients. This program of clinical trials supports the therapeutic use of INPX in the treatment of AIDS and other acquired immunodeficiencies of clinical importance.
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PMID:Isoprinosine (inosine pranobex BAN, INPX) in the treatment of AIDS and other acquired immunodeficiencies of clinical importance. 244 60

Since clinical trials are being planned with the immunomodulating drug isoprinosine combined with the antiviral drug 3'-azido-3'-deoxythymidine (AZT) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex, it is important to determine the type of antiviral interaction produced by these drugs in vitro. Such a combined modality may not only produce enhanced antiviral effects but also may have a valuable immunorestorative action. The interaction of several ratios of AZT and isoprinosine on the replication of human immunodeficiency virus type 1 in human peripheral blood mononuclear cells was determined by reverse transcriptase assay of disrupted virus obtained from supernatants of cells that were exposed to virus and the drugs separately and in combination and by a human immunodeficiency virus type 1 p24 enzyme immunoassay of the same supernatants. The correlation between the reverse transcriptase and enzyme immunoassay data was high. The antiviral activity of AZT alone was neither diminished nor augmented when AZT was used in combination with isoprinosine. Isoprinosine did not enhance virus yield when used alone or in combination with AZT in peripheral blood mononuclear cells, nor did it affect the growth of uninfected cells. The in vitro results indicate that this combination did not decrease the efficacy of AZT or exacerbate virus replication.
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PMID:Combinations of isoprinosine and 3'-azido-3'-deoxythymidine in lymphocytes infected with human immunodeficiency virus type 1. 246 87

Secondary T-lymphocyte deficiencies are common in cancer, aging, malnutrition, chronic infection, and AIDS. Reconstitution with thymic hormones has not been successful. The various thymic hormone preparations induce prothymocyte differentiation and promote the differentiated functions of mature T cells, but they do not regulate intrathymic maturation. In contrast, interleukin 2, endotoxin, thymic epithelial cell products, but not interleukin 1 were found to promote functional maturation of immature thymocytes. Logically, thymic hormones may have synergistic interaction with inducers of intrathymic maturation, and preliminary evidence in athymic nude mice supports this notion. Two classes of drugs show thymomimetic actions. Levamisole, diethyl dithiocarbamate, and other sulfur-containing compounds restore T-cell function via induction of a thymic hormone-like factor. Isoprinosine, NPT 15392, and related hypoxanthine derivatives induce T-cell maturation directly and promote T-cell function in vitro and in vivo. An assessment of the combined actions of these drugs and biologicals should improve immunorestoration in T-cell deficiencies.
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PMID:Correction of secondary T-cell immunodeficiencies with biological substances and drugs. 331 49

Isoprinosine has been reported to decrease progression to AIDS, primarily by preventing Pneumocystis carinii pneumonia (PCP), in human immunodeficiency virus-infected patients, but the mechanism of action is unknown. para-Acetamidobenzoic acid (PAcBA), one component of isoprinosine, is structurally related to para-aminobenzoic acid (PABA), a precursor of de novo folate synthesis. This pathway is known to be important for P. carinii because sulfonamides, which are effective anti-P. carinii agents, inhibit incorporation of PABA into folate precursors by the enzyme dihydropteroate synthetase (DHPS). Inhibition of P. carinii DHPS by PAcBA was investigated by using two assays. In short-term cultures of P. carinii from rats, [3H]PABA incorporation into reduced folates was inhibited by both isoprinosine (mean +/- standard error 50% inhibitory concentration [IC50], 20 +/- 8.4 microM) and PAcBA free acid (IC50, 240 +/- 100 microM); a soluble PAcBA salt was more potent than PAcBA free acid alone (IC50, 29 +/- 48 microM). The activity of PAcBA free acid was confirmed in a cell-free DHPS inhibition assay (IC50, 120 +/- 120 microM). Inosine and dimethylaminopropanol, two other components of isoprinosine, were poor inhibitors of PABA incorporation (IC50, > 1,000 microM). PAcBA free acid also showed activity in inhibiting the DHPS of Toxoplasma gondii, but was a poor inhibitor of the DHPSs of Escherichia coli and Saccharomyces cerevisiae. In a rat model of PCP, the PAcBA salt administered intraperitoneally demonstrated no activity against established PCP either alone or when used in combination with trimethoprim; the lack of efficacy in this model may be due to the rapid metabolism of the drug. Prevention of PCP by PaCBA through inhibition of P. carinii DHPS may explain the activity of isoprinosine in decreasing the progression to AIDS in human immunodeficiency virus-infected patients.
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PMID:Inhibition of Pneumocystis carinii dihydropteroate synthetase by para-acetamidobenzoic acid: possible mechanism of action of isoprinosine in human immunodeficiency virus infection. 768 20