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)

The sedative/hypnotic thalidomide was withdrawn from the worldwide market nearly 40 years ago, because of its teratogenic and neurotoxic effects. Thalidomide was later found to very effectively suppress erythema nodosum leprosum (ENL). The US Food and Drug Administration (FDA) has approved Thalomid (thalidomide) capsules for the acute treatment of the cutaneous manifestations of moderate to severe ENL. Thalidomide is currently under investigation for the treatment of a wide variety of diseases, including conditions thought to have an inflammatory or immune basis, malignancies and complications of infection with HIV. Interest in the potential anti-inflammatory, immunomodulatory and anti- angiogenic effects of thalidomide has resulted in off-label use of prescription thalidomide. During the first 18 months of spontaneous postmarketing adverse event surveillance for Thalomid, 1210 spontaneous postmarketing adverse event reports were received for patients treated with prescription thalidomide for all therapeutic indications, including off-label use. The most common adverse events spontaneously reported would have been expected on the basis of the current Thalomid labelling/product information. The current labelling/product information reflects what was known about the risks associated with thalidomide therapy in limited patient populations at the time of the approval of Thalomid. With the postmarketing use of thalidomide in populations other than patients with ENL, it becomes increasingly important to identify patient groups that may be particularly susceptible to specific adverse drug effects and to identify conditions under which specific adverse events may be more likely to occur. Oncology patients may represent a patient population with increased susceptibility to thalidomide-associated adverse effects, including thromboembolic events. Consideration of the spontaneous postmarketing safety surveillance data may help to identify and characterise factors associated with increased risk in this and other patient groups. Serious unexpected adverse events reported with sufficient frequency to signal previously undetected product-event associations for which there may potentially be plausible evidence to suggest a causal relationship have included seizures and Stevens-Johnson syndrome. The potential effects of thalidomide on wound healing are also being closely monitored. Premarketing human clinical trials of drug products are inherently limited in their ability to detect adverse events. Broader postmarketing experience with thalidomide in more varied patient populations and more experience in the setting of long term thalidomide use will increase our ability to detect rare adverse events and to identify signals that may need to be evaluated in more controlled settings.
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PMID:Thalomid (Thalidomide) capsules: a review of the first 18 months of spontaneous postmarketing adverse event surveillance, including off-label prescribing. 1123 21

Thalidomide has been reported to be an effective therapy for painful oral (mouth) ulcerations associated with AIDS that do not respond to the usual treatment options available. Thalidomide was first developed and marketed in Germany in the 1950s as a sedative. It was withdrawn in 1962 when it was recognized to cause birth defects. Possessing no antibacterial activity, thalidomide is now used to treat a variety of diseases with an autoimmune character. It is unclear how it works to modulate the immune system or whether or not it will accelerate the deterioration of the immunological status of HIV-positive patients. One study suggests that it may suppress HIV viral replication and decrease viral burden. Thalidomide inhibits tumor necrosis factor (TNF). It affects the nervous system, often causing side effects such as drowsiness, dizziness, decreased libido and mood changes, as well as peripheral neuropathy. However, most of the neuropathy cases occurred in patients who had received a high dose for longer than six months. Response to thalidomide occurs at doses ranging from 100mg a day to 400 mg a day, with ulcer pain resolving within two to four days. Randomized placebo-controlled, double-blinded studies are needed to evaluate the efficacy of thalidomide in HIV-positive persons with aphthous ulcers. The AIDS Clinical Trials Unit is doing a six month study comparing thalidomide to placebo for treatment of aphthous ulcers of mouth and esophagus.
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PMID:Thalidomide: an alternative therapy for treatment of apthous ulcers (canker sores). 1136 97

Thalidomide is currently under investigation for its proposed value in treating a number of AIDS-related conditions. Banned in the 1960s because it was found to cause birth defects, thalidomide has been found to inhibit tumor necrosis factor (TNF), a cytokine associated with the development of aphthous ulcers, dementia, fevers, fatigue and wasting, as well as enhanced HIV replication. Development rights to use the drug are owned by Celgene, which calls the drug Synovir. Celgene is currently developing several new TNF inhibitors which are chemically analogous to thalidomide but which might be safer or more effective. Currently, at least 38 sites around the country are testing thalidomide for HIV-related ulcers, and six trial sites are testing for wasting syndrome. Thalidomide is in trials for the treatment of primary HIV infection at five sites. However, it is unclear whether thalidomide does more to curb HIV activity beyond inhibiting TNF. Thalidomide trials have been slow to recruit, therefore buyers clubs are working to make the drug available through their services.
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PMID:Thalidomide and HIV: several possible uses. 1136 2

Three clinical trials of thalidomide in people with AIDS are currently underway in the U.S., evaluating it as a treatment for aphthous ulcers, primary HIV infection, or wasting syndrome. The drug inhibits tumor necrosis factor alpha (TNF) production and release. (TNF may play a role in wasting syndrome and can activate latent HIV in cells.) Thalidomide may also be studied for a number of other AIDS-related indications, such as MAC, Kaposi's sarcoma (KS), and lymphomas. In addition, Celgene (the exclusive licensee of a thalidomide use patent filed by Rockefeller University) is developing new analogs of thalidomide that may be more potent and less toxic, although likely more costly. In addition, the Food and Drug Administration (FDA) has been warning buyers clubs not to sell thalidomide. The buyers clubs are cautiously providing access to the drug, but there are requirements: individuals must have a prescription; individuals must have read and signed a booklet on how to use thalidomide safely; and individuals must agree to return any unused medication. A meeting between the buyers clubs and FDA officials is set for the third week in June to discuss thalidomide.
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PMID:Growing interest in thalidomide. 1136 14

Thalidomide (Synovir), noted for causing severe birth defects when taken by pregnant women, can effectively and safely heal serious mouth ulcers (oral aphthous ulcers) in people with HIV infection. Interim results from a study supported by the National Institute of Allergy and Infectious Diseases (NIAID) show that ulcers healed in 14 of 23 people taking 200 mg/day oral thalidomide compared to only 1 of 22 people receiving placebo. Celgene Corporation is conducting a multicenter, double-blinded, placebo-controlled study of Synovir for the treatment of wasting syndrome. Participants will receive the drug for free, and will take one of three doses: 10, 50, or 200 mg. Interested parties should call the Healing Alternatives Foundation or the PWA Health group.
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PMID:Thalidomide for mouth ulcers and wasting. 1136 16

Thalidomide is being tested as an anti-HIV drug, a weight loss treatment, an immune system regulator, a tuberculosis treatment supplement, and a treatment for microsporidiosis. It is also an effective treatment for aphthous ulcers. Four thalidomide trials are now enrolling and two buyers' clubs are importing the drug from Brazil.
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PMID:Treatment for weight loss, tuberculosis and AIDS? 1136 21

An interim analysis of data from a NIAID-supported study determined that thalidomide effectively and safely heals severe mouth ulcers in persons with HIV infection. The study compares the effectiveness and safety of thalidomide with placebo for treating patients with severe oral and esophageal ulcers. Current and newly-enrolled study participants with oral ulcers will all receive open-label thalidomide rather than being randomized to placebo. Patients with esophageal ulcers will continue to be randomized. Thalidomide is known to cause deformities in infants borne to pregnant women taking the drug.
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PMID:Thalidomide effective treatment for AIDS-related mouth ulcers. 1136 50

Even with the introduction of highly active antiretroviral therapy (HAART), the expected eradication of HIV wasting syndrome has not materialized. Patients who gain weight on HAART seem to gain it as fat, with the body apparently unable to restore lean body mass, even with strenuous exercise programs. It may be that in addition to HAART, an anabolic or anti-inflammatory agent may be needed to reset body chemistry that was damaged by HIV. Serostim, Serono's brand of growth hormone, has been approved to treat wasting, and although it does seem to increase lean body mass and decrease fat in some patients, many patients were not compliant with taking the drug. Testosterone and anabolic steroids were also effective in causing weight gain. Thalidomide is being studied to attack the underlying cause of wasting, namely the overproduction of tumor necrosis factor alpha. In studying thalidomide, however, viral load went up slightly, and reduction of tumor necrosis factor levels was not documented; side effects included skin rash and sleepiness. Research is continuing in this area, with the need to use body composition measurements as a means to gain faster approval of therapies for wasting.
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PMID:No attrition in research on wasting therapies. 1136 78

Chronic diarrhea is a common symptom in HIV-positive persons, much of it due to microsporidia infections. Several drugs are used to treat diarrhea, but the infection is frequently not cleared and the symptoms recur. Thalidomide (Synovir) has been tested in eighteen patients who did not respond to other therapies. Thirty-eight percent achieved complete clinical remission, significant weight gain, and improved results of intestinal biopsies. Thalidomide is an experimental drug currently used for oral aphthous ulcers and wasting syndrome, and is the same drug associated with severe fetal abnormalities in the 1960s.
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PMID:Thalidomide shows benefit for microsporidial diarrhea. 1136 6

Thalidomide is being investigated for its potential use in treating HIV wasting syndrome and other HIV-related conditions. Thalidomide is primarily broken down by hydrolysis; however, the metabolite responsible for its clinical effect is unknown. The optimum concentration of thalidomide or its metabolites to maximize benefits while minimizing toxicities is also unknown. Once daily administration is feasible because of thalidomide's 14- to 18-hour half-life. Because of thalidomide's known potential for causing birth defects, pregnant women are cautioned not to take the drug. One of the two thalidomide stereoisomers was presumed to be responsible for teratogenicity; trials using each isomer individually do not support this notion.
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PMID:Clinical pharmacology of thalidomide. 1136 75


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