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)

Several dideoxynucleosides, including 3'-azido-2',3'-dideoxythymidine (zidovudine, azidothymidine, AZT), 2',3'-dideoxycytidine (ddC), and 2',3'-dideoxyinosine (ddI), have been shown to be potent inhibitors of human immunodeficiency virus (HIV) replication in human T cells and macrophages. These compounds undergo anabolic phosphorylation within target cells to a 3'-triphosphate moiety; as triphosphates, they act at the level of HIV DNA polymerase (reverse transcriptase). AZT has been shown to reduce the morbidity and mortality of patients with severe HIV infection and to at least temporarily ameliorate certain cases of HIV-induced dementia. In phase 1 studies, ddC and ddI have been shown to induce immunologic and virologic improvements in patients with AIDS or related disorders; phase 2 studies of ddC and ddI are underway. The use of these drugs can be associated with toxicity. AZT can cause bone marrow toxicity or myositis with prolonged use, ddC can cause peripheral neuropathy at high doses, and ddI can cause sporadic pancreatitis and peripheral neuropathy at high doses. For each compound, however, a therapeutic window exists in which an anti-HIV effect can be attained without short-term toxicity in most patients. Dose-intensity appears to be an important determinant of the toxicity of dideoxynucleosides. Studies are underway to explore how the therapeutic profiles of these compounds may be enhanced by attention to scheduling or through the use of combination therapy.
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PMID:Initial clinical experience with dideoxynucleosides as single agents and in combination therapy. 207 27

Zidovudine (azidothymidine, AZT), a potent antiviral agent acting on acquired immunodeficiency syndrome virus, was examined with regard to permeation through rat and human skin. A steady state plasma concentration of AZT after transdermal application in rats estimated from both pharmacokinetics data after i.v. administration and penetration rate through excised rat skin from 10% oleic acid (OA) aqueous solution shows penetration about 85 times higher compared to that from 10% OA would be needed for therapeutic efficacy. A mixed-solvent system consisted of 5% Sefsol-318 (S-318), 10% OA, 10% N-methyl-2-pyrrolidone (MP), 20% propylene glycol (PG) and water showed promising characteristics as a vehicle in terms of permeability of AZT through excised rat skin. The maximum flux of 0.41 mumol/cm2/h was observed in excised human skin after application of a gel formulation including S-318, OA, MP and PG. The result suggests a possible use of the gel formulation to gain an effective plasma concentration in humans.
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PMID:Enhanced transdermal delivery of zidovudine in rats and human skin. 208 92

The thymidine analogue 3'-azido-3'-deoxythymidine is an effective inhibitor of HIV replication in vitro and is used in the treatment of acquired immunodeficiency syndrome. We report here upon a rapid sensitive radioimmunoassay for the detection of azidothymidine in serum or plasma. The assay is simple to perform and levels as low as 1 ng azidothymidine/ml can be detected. The assay is specific for azidothymidine and shows almost no cross-reaction with closely related nucleoside analogues or with naturally occurring nucleosides. Using this radioimmunoassay we were able to measure the azidothymidine levels in the serum of monkeys and acquired immunodeficiency syndrome patients treated with AZT. Individual variation in the peak serum level and clearance rate of azidothymidine were seen, which emphasizes the need to tailor the dose to the individual.
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PMID:Serum levels and catabolism of 3'-azido-3'-deoxythymidine in vivo measured using a specific radioimmunoassay. 208 97

In 4 years (1984-1987), 183 bone marrow examinations were performed on 155 human immunodeficiency virus (HIV) antibody positive patients. One hundred and fifty three had category IV AIDS. One-third of the marrows yielded specific information. This included opportunistic infection, in particular Mycobacterium Avium Intracellulare Complex (MAI) (24%), malignancy (4%), consistent with ITP (9%) and iron deficiency (1%). In the remaining two thirds of the bone marrows the most frequent non-specific abnormalities were dyserythropoiesis, erythroid hypoplasia, reticuloendothelial iron block, granulomas, lymphoid aggregates, plasmacytosis and histiocytosis. Common peripheral blood findings were anemia, lymphopenia, anisocytosis, rouleaux and atypical lymphocytes. Peripheral blood and bone marrow examinations on 16 patients on AZT are included. These patients have more pronounced blood and bone marrow abnormalities. The causes of these abnormalities are multifactorial and include low T4 levels, severe viral and other infections and therapy with marrow toxic drugs.
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PMID:Peripheral blood and bone marrow findings in patients with acquired immune deficiency syndrome. 209 Oct 4

The mode of transmission of AIDS is via sexual intercourse, injection of drugs, and from infected mother to child. Incubation time averages 11 years according to the latest studies. Survival after the development of the disease amounts to 14.4 months in the U.S., only 11% live longer than 3 years. Treatment with AZT can prolong survival by months. An effective drug or a vaccine is not in sight, and the reliability of the human immunodeficiency virus (HIV) antibody test has been questioned. There were 4544 AIDS cases reported to the German AIDS registry as of February 28, 1990; and there were 4653 cases as of March 31, 1990. The risk groups are homosexuals (70%), iv drug abusers, and heterosexual partners of infected persons. In the last 6 months there were 3,341 new cases of infection reported, and assuming that only 50% are tested, there are approximately 14,000 new infections per year. Among blood donors there were 2 cases/100,000 in 1987, but high risk individuals have been excluded from giving blood. In the US there were about 1 million infected people; there were 121,645 cases reported at the end of February, 1990. It is estimated that there will be 52,000-57,000 new cases in 1990, and 61,000-89,000 cases in 1993. The Centers for Disease Control conducts several hundred studies in risk areas; there were 6.4% positive tests from 2.5 million tests taken at 5013 counselling and test centers. In some part of New York and Miami over 3% of neonates are infected. In Kampala, Uganda, up to 10% of pregnant women were infected in 1985 and up to 24% in 1987. At the end of February 1990 there were 222,740 AIDS cases reported: 121,645 in the US, 9555 in Brazil, and 8883 in France. In the early 1980's there were about 100,000 infected worldwide, and today they are more than 6 million. It is estimated that at the end of 1989 there were 100,000-150,000 HIV infected in Germany.
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PMID:[Dimensions of the challenge introduced by HIV and AIDS]. 209 75

We evaluated the incidence of AIDS dementia complex (ADC) in groups of patients who acquired infection through different risk behaviours, and attempted to evaluate the possible role of zidovudine (AZT) treatment in preventing or delaying the onset of ADC. The Italian National AIDS Registry was used to study patients with AIDS for whom ADC was reported as an index disease. Relative risk of presenting ADC between different patient categories has been determined. Logistic regression was used to analyse temporal trends in the proportion of AIDS cases presenting with ADC. Of the 6466 cases reported between August '87 and August '90, ADC was seen in 640 (9.9%). I. V. drug addicts had twice the risk (estimated odds ratio: 1.9; 95% confidence interval: 1.5-2.6, p less than 0.001), compared to homo/bisexuals, of presenting with ADC. There is significant evidence (p less than 0.0001) that after a progressive increase in the period '87-'89, it began a definite decrease in the monthly proportion of ADC cases, starting August '89. AZT was introduced in Italy in July 1987 for patients with AIDS or advanced ARC. The incidence of AIDS dementia complex at the moment of AIDS diagnosis in our population of patients, began to decline 24 months after the introduction of systematic AZT treatment in Italy. This could have been due to inhibition of HIV replication in the Central Nervous System among patients who initiated AZT-treatment before developing full-blown AIDS.
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PMID:[Decrease in notifications of AIDS dementia complex in 1989-1990 in Italy: possible role of the early treatment with zidovudine]. 209 87

Data on the number of AIDS cases reported to the Centers for Disease Control (CDC) from January 1984 to June 1989 are used to predict the number of AIDS cases that will be diagnosed during the years 1989 through 1993. Using quadratic and linear models with the most recent data, it is projected that about 44,000 cases will be diagnosed in 1989, 56,000 in 1990, 70,000 in 1991, 87,000 in 1992, and 104,000 in 1993. These projections are lower than estimates derived using data from January 1984 to June 1988, and they are similar to estimates derived by the CDC. The lifetime medical care cost of treating a person with AIDS is estimated to be about $75,000 (all estimates are in 1988 dollars) assuming that the average length of survival is 15 months and that the intensity of care (that is, the cost of medical care per month) does not fall as longevity rises. This total, $75,000, reflects recent increases in the length of survival and the diffusion of costly drug therapies (for example, AZT and aerosol pentamidine). This study forecasts that the cumulative lifetime medical care costs of treating all people diagnosed with AIDS during a given year to be about $3.3 billion in 1989, $4.3 billion in 1990, $5.3 billion in 1991, $6.5 billion in 1992, and $7.8 billion in 1993.
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PMID:Updated forecasts of the costs of medical care for persons with AIDS, 1989-93. 210 97

Ninety-seven isolates of human immunodeficiency virus (HIV) from 73 individuals were assayed for susceptibility to zidovudine (AZT). All isolates from 41 individuals with no known therapy with zidovudine were uniformly susceptible to the drug in vitro. In contrast to isolates from subjects with AIDS or AIDS-related complex, isolates from subjects with fewer signs and symptoms or high CD4 lymphocyte counts developed reduced susceptibility at slower rates and lower levels of resistance. Patients receiving lower doses of zidovudine at both early and late stages of disease did not develop resistance more readily than patients receiving higher doses of drug.
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PMID:Effect of stage of disease and drug dose on zidovudine susceptibilities of isolates of human immunodeficiency virus. 211 76

Infection of macaque monkeys with simian immunodeficiency virus (SIV) has been established as an excellent animal model system for studying the pathogenesis of an HIV-like virus and for evaluating newly developed antiretroviral drugs and vaccines. Based on their genetic, antigenic, and biologic properties, the simian immunodeficiency viruses are the closest known relatives of the human AIDS viruses, and experimental infection of macaque monkeys results in a disease that is remarkably similar to human AIDS. Infected macaques show diarrhea, weight loss, hematologic abnormalities including lymphopenia and thrombocytopenia, lymphadenopathy/lymphoid hyperplasia that progresses to lymphoid depletion, immunosuppression with marked reduction in CD4+ cells and in the CD4+/CD8+ cell ratio, and opportunistic infections. A majority of such macaques die from an AIDS-like disease within one to three years of infection. An acutely lethal variant of SIV has been identified that results in death in susceptible macaques within 7-12 days of infection. Preliminary prophylactic treatment trials with AZT in macaque monkeys exposed to the acutely lethal SIV variant indicate that some protection is provided when AZT treatment is initiated within 24 hours of virus exposure. Other studies with the more chronic SIV infection model, however, failed to show any prophylactic efficacy of CS-87, AZT, D4T, or FDT.
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PMID:Nonhuman primate models for evaluation of AIDS therapy. 212 64

Two methods used to forecast AIDS cases--trend analysis and back calculation--are examined in this paper. I forecast AIDS cases using trend analysis with data on the number of cases reported between January 1984 and March 1990. Forecasts using back calculation methods are based on the assumption that the progression rates from HIV to AIDS slowed in 1988 due to the use of AZT and aerosol pentamidine. With both methods, reasonable models yield widely different forecasts. Analysis also is hampered by a lack of information about the basic determinants of AIDS incidence, changes in the definition of AIDS, underreporting, and uncertainty about the effect of the use of prophylactic drugs. It is not possible to establish confidence limits around forecasts that take into account these sources of biases, and it is important that those who use AIDS forecasts be aware of these uncertainties.
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PMID:Forecasting the number of AIDS cases: an analysis of two techniques. 214 22


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