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)

Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other antiretroviral agents. The population pharmacokinetics and pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected, antiretroviral naive adults with baseline CD4(+) cell counts of >/=100/mm(3) and plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained from patients who received randomized, blinded monotherapy with abacavir at 100, 300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir concentrations from sparse sampling were analyzed by standard population pharmacokinetic methods, and the effects of dose, combination therapy, gender, weight, and age on parameter estimates were investigated. Bayesian pharmacokinetic parameter estimates were calculated to determine the peak concentration of abacavir in plasma (C(max)) and the area under the concentration-time curve from time zero to infinity (AUC(0-infinity)) for individual subjects. The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg dose range and were unaffected by any covariates. No significant correlations were observed between the incidence of the five most common adverse events (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC(0-infinity). A significant correlation was observed between C(max) and nausea by categorical analysis (P = 0.019), but this was of borderline significance by logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32). The log(10) time-averaged AUC(0-infinity) minus baseline (AAUCMB) values for HIV-1 RNA and CD4(+) cell count correlated significantly with C(max) and AUC(0-infinity), but with better model fits for AUC(0-infinity). The increase in AAUCMB values for CD4(+) cell count plateaued early for drug exposures that were associated with little change in AAUCMB values for plasma HIV-1 RNA. There was less than a 0.4 log(10) difference over 12 weeks in the HIV-1 RNA levels with the doubling of the abacavir AUC(0-infinity) from 300 to 600 mg BID dosing. In conclusion, pharmacodynamic modeling supports the selection of abacavir 300 mg twice-daily dosing.
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PMID:Population pharmacokinetics and pharmacodynamic modeling of abacavir (1592U89) from a dose-ranging, double-blind, randomized monotherapy trial with human immunodeficiency virus-infected subjects. 1089 75

Ritonavir (RTV), a protease inhibitor, and carbamazepine (CBZ), an anticonvulsant, were administered concurrently to a patient who had human immunodeficiency virus infection and epilepsy. The combination resulted in elevated serum concentrations of CBZ, with accompanying vomiting, vertigo, and transient liver dysfunction. After discontinuing RTV and reducing the dosage of CBZ, the serum concentration of CBZ returned to the optimal range, symptoms subsided, and liver function returned to baseline. Carbamazepine is metabolized in the liver to a large extent by the cytochrome P450 (CYP) system, especially CYP3A4, 2C8, and 1A2, whereas RTV is metabolized primarily by CYP3A and is a potent inhibitor of this enzyme. Careful clinical monitoring may help prevent adverse drug interactions when these drugs are administered concurrently.
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PMID:Potential interaction between ritonavir and carbamazepine. 1090 77

Lactic acidosis and hepatic steatosis caused by mitochondrial toxicity of nucleoside reverse transcriptase inhibitors (NRTI) is a rare cause of liver disease with a high mortality rate. This report describes a male, HIV-positive patient with a 4-week history of nausea, vomiting and abdominal pain. His medication consisted of prednisone 5 mg od (because of auto-immune thrombocytopenia), didanosine (for 2 years) and stavudine (for 3 months). Laboratory studies showed cholestasis and elevation of aminotransferases. Lactic level was not measured. Liver biopsy revealed steatosis and cholestatic hepatitis. In the absence of other causes of liver disease a probable diagnosis of stavudine-induced hepatic toxicity was made. After discontinuation of NRTI, he recovered completely. Because lactic acidosis had not been confirmed, stavudine was restarted and within 1 week the lactate level increased significantly. Therefore stavudine was discontinued again. One year later the patient is doing well on a double protease inhibitor regimen. In conclusion, clinicians treating patients with NRTI should be aware of the risk of lactic acidosis and hepatic steatosis. When this is suspected, all NRTI must be stopped. The diagnosis can be made when elevated lactate levels and hepatic steatosis are present in the absence of other causes of liver disease.
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PMID:Hepatic steatosis and lactic acidosis caused by stavudine in an HIV-infected patient. 1106 65

A 40-year-old HIV-infected woman developed nausea, vomiting, and epigastric pain and died following her third dose (per study protocol) of interleukin (IL)-2. Her HIV infection was diagnosed in 1996. Her last CD4 cell count was 390/microL, and her viral load was negligible (as of November 28, 1998). She had no known general risk factors for thrombosis other than HIV infection, injection drug abuse, and antiretroviral therapy with indinavir. Abdominal films showed no sign of mechanical obstruction but a generalized gas distention of the bowel, which was suggestive of paralytic ileus. Autopsy revealed dilation of the small bowel with extensive necrosis and hemorrhage involving all the segments. The superior and inferior mesenteric arteries revealed severe atherosclerosis. The stenotic celiac artery was occluded by a recent thrombus at the aortic ostium. Clinicians need to be aware of the potential for thrombosis and accelerated atherosclerosis in HIV-infected patients. Both injection drug abuse and protease inhibitors, such as indinavir, have been shown to be risk factors for thrombosis. However, it is likely IL-2 contributed to the severe thrombosis in this patient, although definitive proof is lacking. An acute awareness of intestinal infarction in HIV-infected patients is warranted.
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PMID:Case report. Intestinal infarction due to vascular catastrophe in an HIV-infected patient. 1118 43

Seroconversion to human immunodeficiency virus(HIV) associated with an illness characterized by fever, sore throat, and lymphadenopathy, sometimes with rash, diarrhea, and vomiting. Leukopenia and liver dysfunction also can occur in some patients. The antibody response associated with HIV infection is directed against a variety of viral proteins. Western blot analysis(WB) is used currently for determining HIV-1 infection. A 47-year-old man whose wife was infected with HIV was found to have contracted primary HIV infection. His first HIV antibody examination 4 weeks after speculated exposure was negative by particle agglutination(PA) method and WB. Approximately 2 weeks later he experienced fever, general fatigue, oral candidiasis. His second laboratory examination showed positive PA and indeterminate WB tests, an HIV-RNA PCR of 4.4 x 10(5) copies/ml, 223 CD4+ lymphocytes/microliter, and liver dysfunction. Two weeks later, all of his symptoms and the abnormal lab data had improved with antifungal therapy alone and no anti-HIV therapy. Subsequently, it took 16 more weeks before HIV infection could be diagnosed by WB. It is necessary to adopt an appropriate HIV-1 PCR method to shorten the diagnostic window in primary HIV infection.
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PMID:[A case of primary HIV infection with oral candidiasis not diagnosed by western blot]. 1130 31

The nucleoside reverse transcriptase inhibitor 3TC (lamivudine) appears to induce unusually prolonged HIV suppression when used in combination with AZT, according to the results of four randomized clinical trials. The studies showed that 3TC and AZT had similar antiviral effects when used alone. However, investigators observed a substantial, prolonged increase in CD4 counts and a significant decrease in HIV RNA when the drugs were administered simultaneously. These benefits persisted in all study groups for the 24-week study period, and in several for the six-month follow-up period as well. The combination was well-tolerated by nearly 1000 AZT-naive and AZT-experienced subjects enrolled in these trials, with the most common adverse effects being nausea, vomiting and headaches. A possible explanation for the antiviral effect is suggested by the mutation at HIV codon 184 that is frequently observed in virions exposed to 3TC for extended periods of time. In vitro studies have shown that this mutation confers 3TC resistance. It may also counteract other mutations that would normally lead to AZT resistance, therefore enabling virions exposed to both drugs to remain effectively susceptible to AZT.
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PMID:Combination 3TC/AZT therapy shows promise. 1136 92

The Centers for Disease Control and Prevention (CDC) recommends that immunocompromised people avoid exposure to cryptosporidium in outbreak settings by drinking water that is boiled, filtered, or bottled. A parasite, cryptosporidium is spread when persons ingest infected feces of humans or animals, or eat raw or undercooked vegetables contaminated with an egg-like form of the parasite. Symptoms include watery diarrhea, headache, abdominal cramps, nausea, vomiting and low-grade fever; in immunocompromised patients infection often leads to weight loss, dehydration, and may become life-threatening. Drugs can treat the symptoms, although cryptosporidiosis is not curable and often recurs in severely immunocompromised patients. To prevent becoming infected; HIV-positive people should not drink water from lakes, rivers, and swimming pools; avoid unpasteurized milk or milk products; wash hands after contact with pets or with soil; and follow safe-sex guidelines. The CDC also recommends that in settings with an outbreak of cryptosporidium, individuals boil water for one minute to kill the parasite or use a filter for tap water that is capable of removing particles less than one micron in diameter. A third option is to use bottled water for drinking, although it is difficult to know which is safe since no organization regulates it.
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PMID:CDC provides guidelines on suspect water supplies. Centers for Disease Control and Prevention. 1136 76

A three-judge panel of the Ohio Court of Appeals dismissed the lawsuit of a man who sued a hospital for breach of confidentiality of his positive HIV status. The patient, John Doe, presented at an Ohio State University Hospital with severe pain and vomiting. He was referred back to his regular physician, Dr. [name removed], who ordered a battery of tests. The laboratory inadvertently performed an HIV-antibody test, found that Doe was infected, and sent his name to the Ohio Department of Health. John Doe sued the University, alleging that it had violated a state law which requires informed consent for HIV-antibody testing. The trial judge found in favor of the University. The appeals panel affirmed the lower court's decision, stating that the case was not one of negligence, but rather an allegation concerning the informed consent statute. The Court stated that an individual could only file for compensatory damages if the person or agency knowingly violated the requirement for informed consent.
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PMID:Law wasn't broken if test was done by accident. 1136 61

The Food and Drug Administration's (FDA) Antiviral Drugs Advisory Committee met February 27 to March 1, 1996. At the meeting, the FDA granted full approval of ritonavir for the treatment of advanced AIDS. Ritonavir manufacturer, Abbott Laboratories, characterized the drug as generally well-tolerated, with the most common side effects being nausea, vomiting, and diarrhea. The committee also recommended accelerated approval of Merck's protease inhibitor, indinavir. Results of several clinical studies and protocols are presented. The committee voted against somatropin (Serostim), the recombinant human growth hormone, for treatment of AIDS-related wasting syndrome. They cited too many gaps in the research data. The manufacturer, Serono, is currently negotiating with the FDA on the best way to pursue approval. The committee also unanimously recommended that ddI (Videx) be indicated as a first-line treatment for HIV. The drug appears to be superior to AZT in delaying disease progression and death.
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PMID:Highlights from the FDA antiviral drug advisory committee meetings, February 27-March 1, 1996. 1136 21

Ritonavir (Norvir), a protease inhibitors, was approved for HIV treatment by the Food and Drug Administration (FDA). Studies have shown that ritonavir helps people live longer and delays the progression of the illness. One study showed that the death rate for the treated group was half that of the group taking a placebo. Ritonavir should be taken with meals. Many people cannot tolerant the side effects, including nausea, vomiting, weakness, diarrhea, elevated liver enzymes, and numbing around the mouth. Ritonavir affects the way other drugs are absorbed by the body, and its use should be closely monitored for toxic reactions.
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PMID:Ritonavir (Norvir). 1136 97


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