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)

DMP 323 is a symmetrically substituted cyclic urea compound with demonstrated activity against human immunodeficiency virus (HIV) in vitro. DMP 323 has been measured in rat and dog plasma via liquid-liquid extraction and HPLC. The limit of quantitation is 10 ng/ml using 0.5 ml plasma. Following an intravenous dose of 5 mg/kg to rats, DMP 323 exhibited an apparent volume of distribution at steady-state of 6.36 liters/kg and clearance of 7.12 liters/hr/kg. The same dose administered intravenously to dogs resulted in apparent volume of distribution at steady-state and clearance values of 2.28 liters/kg and 1.48 liters/hr/kg, respectively. Elimination half-lives were 0.95 hr in rats and 1.80 hr in dogs. DMP 323 was rapidly absorbed from oral solution doses in rats (3, 5, and 10 mg/kg) and dogs (5 and 10 mg/kg), achieving maximum plasma concentrations in 1 hr or less in both species. Absolute bioavailability of DMP 323 from oral doses ranged from 15 to 27% in rats and from 37 to 38% in dogs. Pharmacokinetics were unchanged in rats and dogs over 8-day t.i.d. and 5-day b.i.d. multiple oral dose regimens, respectively. Oral doses administered to fed animals resulted in lower plasma concentrations of DMP 323 than the same doses administered to fasted animals. Because of its in vitro high potency and acceptable pharmacokinetics, DMP 323 seems to be a worthy candidate for further study in the effort to develop an inhibitor of HIV protease for use in the therapy of AIDS.
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PMID:Pharmacokinetics of HIV protease inhibitor DMP 323 in rats and dogs. 783 21

It was recently shown that peptide NTM (RSANFTDNAKTIIVQLNESV), corresponding to residues 280-299 in the second conserved domain of HIV-1 envelope glycoprotein gp120, has spectral and sequence similarity with human vasoactive intestinal peptide, VIP (Veljkovic et al., Biochem. Biophys. Res. Commun., 189, 705-710, 1992). We found that natural autoantibodies cross-reactive with this peptide can be detected in sera from HIV-negative asthma patients and healthy blood donors. The level of these antibodies is significantly higher in asthma patients than in healthy individuals, suggesting that these antibodies can in fact be at least partly identical to natural anti-VIP antibodies previously described (Paul et al., Biochem. Biophys. Res. Commun., 130, 479-483, 1985; Paul et al., Science, 244, 158-1162, 1989). Possible origin and role of these antibodies in AIDS pathogenesis and therapy are discussed.
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PMID:Natural autoantibodies cross-react with a peptide derived from the second conserved region of HIV-1 envelope glycoprotein gp120. 825 Aug 61

Seminal viral load is likely to be directly related to the sexual transmissibility of human immunodeficiency virus type 1 (HIV-1). However, it is not clear whether the level of HIV-1 in semen varies with the stage of infection and whether antiretroviral therapy reduces seminal viral load. A nucleic acid sequence-based amplification (NASBA) technique was used to quantify HIV-1 RNA as an indicator of infectious viral load in semen and blood plasma of homosexual men with different stages and durations of HIV-1 infection. The median viral load in a cross section of 34 men was 11,000 HIV-1 RNA copies/ml (range, <400 to 1.3 x 10(7) copies/ml) in whole semen and 5,238 HIV-1 RNA copies/ml (range, <400 to 2.8 x 10(5) copies/ml) in seminal plasma, which is 10- to 1,000-fold higher than previous estimates. Viral loads in whole semen and seminal plasma were strongly correlated with blood plasma viral load (P < 0.001) but not with blood CD4+ T-cell count (P = 0.420). Longitudinal analysis of eight subjects who progressed to AIDS showed that seminal viral load increased in most cases, with viral load consistently higher in blood plasma than in semen. Viral loads in semen and blood plasma decreased markedly in six other patients following initiation of potent combination therapy with a protease inhibitor (indinavir) and a nonnucleoside reverse transcriptase inhibitor (DMP-266). These findings have important implications for the biology of sexual transmission of HIV-1 and its potential reduction by antiretroviral therapy.
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PMID:High viral load in semen of human immunodeficiency virus type 1-infected men at all stages of disease and its reduction by therapy with protease and nonnucleoside reverse transcriptase inhibitors. 922 32

Disseminated Mycobacterium avium-intracellulare complex (DMAC) infection is a common complication of AIDS. The cumulative incidence is 40% in patient surviving 2 years after diagnosis of AIDS. AIDS patients with DMAC reduced life expectancy compared with those without. Antimycobacterial therapy with Clarithromycin (CAM) can significantly reduce bacteremia and improve symptoms, quality of life, and survival of patients with DMAC. Prophylactic therapy with Rifabutin, CAM and Azithromycin is effective and Synergic effect can be expected as Rifabutin and Azithromycin are administered together. But it is serious problem to get resistance to CAM when prophylactic therapy with CAM failed because we lose one of the most effective medicines against DMAC. It is recommended to start prophylactic therapy when CD4 Lymphocyte count falls below 50-75/microliters in patients who had opportunistic infection. In Japan, 32 cases of AIDS with NTM are reported. All of them are male and mean count of CD4+lymphocyte was 11/microliters. Twenty three out of 32 were MAC and 6 were M. kansasii. Cases of NTM bacteremia were 9 (69.2%) and cases of those without bacteremia were 4 (30.8%). Three out of 4 were cases of M. kansasii.
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PMID:[Nontuberculous mycobacteriosis; the present status and in the future. Infection with human immunodeficiency virus (HIV) and nontuberculous mycobacteriosis]. 954 2

The appearance in the clinic of two to three new antiretroviral agents yearly since 1995 has permitted unprecedented advances in HIV treatment. This remarkable pace of drug development is a testimony to an extraordinary international effort involving scientists, clinicians, governments, community activists and industry dedicated to the rapid and safe development of novel therapies. New drugs present the opportunity to improve HIV therapy. They also create an enormous challenge to the clinician, who must constantly assimilate data on new drugs and incorporate this information into practical management strategies. Combination therapy has proven the most effective approach to treat HIV disease. The profound and sustained viral suppression achievable with combinations such as indinavir (IDV), lamivudine (3TC) and zidovudine (ZDV) have resulted in a dramatic shift in HIV treatment paradigms over the last year. The full potential of combination therapy with available drugs has yet to be realized as only a limited number of the possible combinations incorporating new drugs have been fully tested. Even drugs available for many years may have untapped potential. Didanosine (ddI) and stavudine (d4T), once thought to be contraindicated in combination because of their overlapping peripheral neuropathy toxicity, have proven well tolerated and effective. Combination therapy can increase antiviral suppression, prevent drug resistance, optimize drug exposure and simplify dosing, but it can also result in pharmacologic antagonism, subtherapeutic drug concentrations and unexpected toxicities. Clinical studies have confirmed in vitro studies showing pharmacologic antagonism for the combination of ZDV and d4T. Combining protease inhibitors with each other or with non-nucleoside reverse transcriptase inhibitors is complicated by effects both classes of drugs have on drug metabolism and clearance. These observations underline the importance of carefully conducted clinical studies to characterize safety, pharmacokinetics and efficacy of combination therapies. In this review, we will first summarize the clinical profile of new drugs which either became commercially available last year [nelfinavir, nevirapine, delavirdine (DLV)] or are in the late stages of clinical development (DMP-266, abacavir and 141W94). Later we will summarize new data on nucleoside, protease inhibitor and non-nucleoside reverse transcriptase combination regimens. Finally, we will briefly mention new drugs in early stages of development.
AIDS 1998
PMID:New antiretrovirals and new combinations. 963 99

As the result of a formidable effort, the recent TB epidemic in the United States has abated; however, major questions remain as the risk of TB diminishes. Will we maintain an adequate public health effort not only to prevent another resurgence of TB but also to renew our pursuit of TB elimination? Do we have the will to extend the fight against TB worldwide as the TB threat in the United States declines? What is the best way to incorporate new diagnostic technology into routine practice? What are the best strategies for preventing and treating TB in AIDS patients? From the standpoint of NTM lung diseases, the major challenges are to educate clinicians about the variety and clinical presentation of NTM lung pathogens in order to recognize NTM lung disease as early as possible and to maximize treatment options. Hopefully, we can also improve upon the recent unprecedented progress in treatment regimens for NTM diseases of all types.
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PMID:Mycobacteria as pathogens of respiratory infection. 977 80

As combination therapy for treating HIV/AIDS grows, data on how these drugs interact becomes necessary and more complex. Information is provided on drug interactions using nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors, NNRTIs and nucleoside reverse transcriptase inhibitors, DMP 266 and indinavir, AZT and delavirdine, and ritonavir and saquinavir. New concerns for some combinations have arisen concerning AZT with d4T and nevirapine with indinavir. Trial results and questions about using these drugs are provided.
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PMID:Antiviral update. 1136 72

Dupont Merck announced that its experimental non-nucleoside reverse transcriptase inhibitor DMP 266 has shown viral load reductions to undetectable levels in eighty percent of study subjects. CD4 counts also increased among the study group. Other studies are underway to study DMP 266 at higher dosages and in combination with other drugs. Enrollment information is included.
Crit Path AIDS Proj 1997
PMID:DMP 266 study opens at Jefferson. 1136 40

DMP 266, a non-nucleoside reverse transcriptase inhibitor (NNRTI) in the same general class as nevirapine or delavirdine, is undergoing clinical trials. Potential advantages of DMP 266 are that it is only taken once a day (making adherence easier for patients), there does not appear to be serious supply problems, and drug resistance appears to develop more slowly than other NNRTIs. Two Phase II trials, DMP 266-20 and DMP 266-006, are now recruiting protease inhibitor-naive persons. The company has decided to offer the drug to volunteers who complete either trial (each lasts 24 weeks) and wish to continue. Details about both trials and contact information are provided.
AIDS Treat News 1997 Sep 05
PMID:DMP 266 trials recruiting, many cities -- protease inhibitor naive. 1136 23

Efavirenz (SUSTIVA, formerly DMP 266), is being made available to AIDS patients who are failing or are intolerant of their current regimen, and who have no other options available. Patients must have a CD4 count less than or equal to 50 within the last 90 days. Excluded concomitant medications and other restrictions are provided. Efavirenz should be used with at least one other antiviral to which the patient has not been exposed, and the failing regimen should be changed entirely. Patients may also be receiving treatment on other expanded access programs. Efavirenz will be provided at no charge, but patients may have to pay for blood work and any other expenses.
AIDS Treat News 1997 Sep 19
PMID:Efavirenz (SUSTIVA) expanded access begins October 1. 1136 89


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