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)

Various nucleoside analogues are being used or are being considered for use as therapeutic drugs to inhibit replication of the HTLV-III/LAV virus in infected human cells. Here, the ability of seven nucleoside analogues, a combination of two analogues, and two other therapeutic compounds to induce genotoxic and cytotoxic damage in vivo was evaluated in the mouse bone marrow micronucleus test. Using a 3-consecutive-day oral treatment protocol, almost all of the test chemicals induced a significant increase in the frequency of micronucleated polychromatic erythrocytes (MN-PCE) in male B6C3F1 mice, ranked in decreasing potency as 6-thioguanine greater than Cytarabine HCl greater than 3'-azido-3'-deoxythymidine (AZT)/2',3'-dideoxycytidine combination = AZT greater than Ribavirin = 2',3'-didehydro-3'-deoxythymidine greater than 2',3'-dideoxyadenosine = 2',3'-dideoxycytidine. The frequency of MN-PCE was not increased significantly by treatment with 2',3-dideoxyinosine (DDI) or pentamidine isethionate (PI). The differential ability of AZT and DDI to induce MN in mouse bone marrow was verified from peripheral blood smears prepared from subchronic (90 day) oral studies. The lack of genotoxic activity by DDI was route-specific since, when tested by intraperitoneal injection, a small but significant increase in MN-PCE was observed. A number of these chemicals induced a significant depression in erythropoiesis. However, there was not a significant correlation between the increase in MN-PCE and the depression in the percentage of PCE. This lack of a correlation suggests that factors other than DNA damage may contribute to the inhibition in the rate of erythropoiesis. The presence of increased levels of micronuclei in bone marrow PCE following treatment with various nucleoside analogues suggests that intrinsic genotoxic activity in mammalian cells should be one factor considered during drug selection for AIDS therapy.
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PMID:Induction of micronuclei in mouse bone marrow cells: an evaluation of nucleoside analogues used in the treatment of AIDS. 191 12

Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a broad-spectrum antiviral agent whose molecular mode of action remains remarkably controversial. This antiviral agent was approved by the U.S. Food and Drug Administration in 1986 for use as an aerosol for infants with serious infections due to respiratory syncytial virus. Ribavirin is and has been under clinical investigation for activity against a variety of viral illnesses, including those due to influenza virus, Lassa fever virus, Hantaan virus, and human immunodeficiency virus (HIV). There has been a great deal of clinical interest in the utilization of ribavirin for treatment of infections due to HIV. It has been reported to slow the development of AIDS in HIV-infected patients. We describe here the major mechanisms of action of this newly licensed antiviral agent.
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PMID:Molecular mechanisms of action of ribavirin. 226 89

We now have a basis for a more rational approach to rapid evaluation and development of antiviral drugs by screening for activity in vitro, testing for toxicity and efficacy in animals, and clinical testing in humans. Acyclovir is a prototype of this improved process. Interferon has a beneficial effect against CMV infection in renal transplant patients and has promising results in the treatment of papillomas and rhinovirus infections. It does not seem to be as effective against genital herpes or varicella zoster as acyclovir. Ribavirin is effective against respiratory syncytial virus infections and Lassa fever. Varicella-zoster virus is highly sensitive to bromovinyl deoxyuridine in vitro. Phosphonoformate is effective in herpes simplex in animals but of little clinical benefit topically in human recurrent A2 herpes. Zidovudine may decrease mortality rates and infectious complications in patients with acquired immunodeficiency syndrome. DHPG (9-(1,3-dihydroxy-2-propoxymethyl]guanine is useful in treatment of cytomegalovirus and infection in immunocompromised patients. The prodrug of acyclovir results in high blood levels of acyclovir and shows promise in the treatment of varicella-zoster infections. Many halogenated pyrimidine nucleoside analogs are being developed. Buciclovir is another acyclic guanosine analog effective against herpes simplex virus in vitro. 2'-nor-cyclic guanosine monophosphate has a broad antiviral spectrum of action. Interleukin-2 is being investigated. Combined therapies of two or more antiviral drugs or antiviral drugs and other treatments are being studied.
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PMID:Promising new antiviral drugs. 244 52

A therapeutic trial is described which concerns 6 patients with AIDS and 6 patients with ARC who were submitted to a 6 month course of Ribavirin. Ribavirin was administered orally as the following doses: 3.000 mg daily the first week, 2.000 mg daily the second 2 weeks, and 1.000 mg daily up to completion of the 6 months period. No major side-effects were recorded; only a transient anemia was observed in almost all patients at the higher dose; none of them, however, required to be transfused. No improvement was shown by any of the 6 AIDS patients, neither clinically nor according to laboratory test, whereas all 6 patients with ARC experienced a sense of well-being, a clearing of their symptoms and an average weight gain of about 2.5 kg. No significant changes, though, were recorded as for their immune parameters. A remarkable drop of aminotransfereas was also observed in 4 of the patients, who were affected with chronic hepatitis as well. We conclude that additional, if any, Ribavirin trials should be carried out only in ARC patients.
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PMID:A trial with ribavirin in patients with AIDS or AIDS-related complex. 249 3

Ribavirin, a broad spectrum, non-interferon-inducing virustatic chemotherapeutic agent, demonstrates activity against a wide range of RNA and DNA viruses, including the retrovirus known to cause the acquired immune deficiency syndrome. The drug's proposed mechanism of action, as well as pharmacokinetics are discussed, and preclinical toxicity, safety and clinical efficacy studies are presented. To date, the best success has occurred in the use of ribavirin to treat respiratory syncytial virus infection in infants and young children and to treat influenza A and B virus infections in young adults. Viral infections, particularly viral pneumonia, are often life-threatening in infants with severe combined immunodeficiency disease (SCID), and ribavirin aerosol has been used successfully to treat respiratory syncytial virus and parainfluenza virus infection of immunodeficient children. Special note is taken of ribavirin's clinical benefit in treating severe and life-threatening infections caused by the Lassa fever virus and the significant improvement over either the use of immune plasma or supportive therapy alone. Indeed, ribavirin thus emerges as the first antiviral drug that is able to reduce mortality in a highly lethal systemic disease by more than 90%. Additional studies demonstrate the drug's efficacy in acute viral hepatitis, herpesvirus infections, and measles. Controlled clinical trials are underway to test the drug in patients infected with the AIDS virus.
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PMID:Ribavirin: a clinical overview. 302 19

Amantadine is well established as the preferred antiviral agent for the prophylaxis of influenza A and may also be beneficial therapeutically when used early in the course of the disease. Idoxuridine is applicable only in the treatment of herpetic keratitis. Currently, acyclovir is the most effective agent for the treatment of herpes simplex and varicella-zoster virus infections. Ribavirin has recently been released for use in aerosol form for severe respiratory syncytial virus infections that occur in infants and young children. Vidarabine, which previously was the drug of choice in the treatment of severe herpetic infections, has now been replaced by the more effective acyclovir. Ganciclovir, an experimental agent, has shown promise against cytomegalovirus infections in patients who have undergone kidney or liver transplantation, but its effects are only temporary in patients who have undergone bone marrow transplantation and patients with acquired immunodeficiency syndrome (AIDS) who have cytomegalovirus infections.
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PMID:Antiviral agents. 350 Mar 76

The current epidemic of acquired immunodeficiency syndrome (AIDS) poses a major threat to our population. Urgently needed are both a vaccine to prevent infection with the etiologic retrovirus, human immunodeficiency virus (HIV), and safe, effective antiviral agents to treat those individuals already infected. The elucidation of viral replicative mechanisms has allowed the development and testing of several agents active against HIV in vitro. Inhibitors of reverse transcriptase that have demonstrated activity include azidothymidine, phosphonoformate, antimoniotungstate (HPA-23), and suramin. Ribavirin and recombinant interferon alpha-A (IFN-alpha-A) also inhibit HIV replication, although their mechanisms of action are less clear. All of these compounds are undergoing early clinical trials in patients with HIV infection. The identification of immunogenic viral proteins may allow the development of one or more subunit vaccines against HIV. Studies are underway to clone appropriate viral genes and incorporate the expressed proteins into vectors for administration. Laboratory models, e.g., chimpanzees, will be inoculated with candidate vaccines and, if successful, this will be followed by clinical trials for safety and efficacy in appropriate human populations seronegative for HIV. Although important problems, such as virus envelope protein variability, need to be addressed, efforts to develop effective vaccines may well prove successful in the years ahead.
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PMID:Prospects for the prevention and therapy of infections with the human immunodeficiency virus. 354 Nov 31

Remarkable progress has been made in antiviral chemotherapy. Six approved antiviral drugs are now available for the treatment of various viral infections. Trifluridine, idoxuridine and vidarabine are all effective in patients with herpes keratitis; trifluridine is preferred due to its low toxicity. Acyclovir is the drug of choice in patients with infections due to herpes simplex viruses, including genital herpes, herpes encephalitis, and neonatal herpes, and infections due to varicella-zoster virus. Amantadine is the only drug currently available for prophylaxis and treatment of influenza A, but an investigational drug, rimantadine, appears to be equally effective and less toxic than amantadine. Ribavirin is the most recently approved antiviral agent for the treatment of respiratory syncytial virus infections. Numerous antiviral drugs are being studied in patients with acquired immunodeficiency syndrome. Although currently available drugs have improved our ability to manage a variety of viral illnesses, much needs to be learned about specific dosage guidelines based on the studies of pharmacokinetics, pharmacodynamics, potential adverse effects and viral resistance, and the role of combination therapy to optimize therapy.
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PMID:Clinical use of antiviral drugs. 355 26

Persistent viral infections have been postulated to be trigger factors for the development of autoimmune disease. We report the development of vitiligo in four patients with human immunodeficiency virus (HIV)-related conditions and in one patient with hepatitis who later developed both psoriasis and acquired immunodeficiency syndrome (AIDS). Other common features were hepatitis and multiple other viral infections. Ribavirin was associated with repigmentation in one patient. Vitiligo may be an example of an autoimmune disease triggered by viral infection in a genetically predisposed host.
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PMID:Human immunodeficiency virus-associated vitiligo: expression of autoimmunity with immunodeficiency? 366 11

This study investigated the in vitro effect of the drug ribavirin on the replication of lymphadenopathy-associated virus (LAV), a prototype virus etiologically associated with acquired immunodeficiency syndrome (AIDS). Ribavirin has been shown to have low toxicity in humans and its effect is reversible when the drug is discontinued. The study data suggest that ribavirin inhibits the replication of LAV in human adult T lymphocytes in vitro. Significant suppression of virus replication was noted at higher drug concentrations (50 and 100 mcg/ml) during the 1st week of infection, although virus replication began to increase on the 8th or 9th day, presumably as a result of degradation of the drug. The data further indicate that ribavirin suppresses viral replication without irreversibly affecting cell function. Although the lowest effective in vitro dose of ribavirin is 30-50 mcg/ml, the in vivo dosage requirement may be different.
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PMID:Ribavirin suppresses replication of lymphadenopathy-associated virus in cultures of human adult T lymphocytes. 615 Mar 68


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