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)

Several studies have been performed to investigate the appropriate dose of efavirenz (SUSTIVA, DMP 266, EFV) for the treatment of HIV infection. When considering the most appropriate dose, virological, pharmacological, clinical and safety data from these studies were examined. Efavirenz 600 mg once daily is the recommended dose of efavirenz for combination therapy in adults. Efavirenz 600 mg once daily adjusted for body size is the appropriate dose for combination therapy in children three years of age or older.
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PMID:Dose-ranging studies. 1062 36

An isothermal microcalorimeter was utilized to characterize a model solid-state interaction. The degradation of the HIV protease inhibitor, DMP 450, in a binary mixture with hydrous lactose was followed in the presence of 5% additional water. Heat produced in the microcalorimeter sample vessel from either chemical or physical change is channeled through extremely sensitive thermopile blankets and is measured as it flows into infinite heat sinks. Solid-state 1:1 mixtures of DMP 450 and hydrous lactose each with 5% water added were analyzed in the microcalorimeter at 50, 60 and 65 degrees C. The resulting heat flow profiles were consistent with an autocatalytic rate law. An activation energy of 26.12 kcal mol(-1) for the DMP 450:lactose mixture was determined from the slope of the Arrhenius plot of the microcalorimetry heat flow maximum value versus the reciprocal of the absolute temperature. The activation energy determined by the traditional method with HPLC analysis was found to be in excellent agreement with the microcalorimetry value at 26.38 kcal mol(-1).
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PMID:Utility of microcalorimetry in the characterization of the browning reaction. 1070 46

Protease inhibitors are widely used in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected individuals and show a drastic effect on the reduction of virus load. We previously reported that doughnut-shaped, protease-defective gp120-containing HIV-1 particles from an L-2 cell clone, carrying a provirus with mutations at the pol (protease), env (gp41) and nef genes, rapidly and more effectively induces virus particle-mediated syncytia formation of uninfected T-cells, than a parental wild-type laboratory strain of HIV-1 (LAI). In this study, we examined the possibility of whether enhanced syncytia formation is mediated by morphologically similar doughnut-shaped particles obtained after treatment of LAI-infected cells with the protease inhibitors L-689, 502, DMP-323, RO-31-8959, and KNI-272. Utilizing such protease inhibitor-induced particles and a clone of MOLT-4 cells, we could not detect any enhancement of syncytia formation, over that seen with wild-type LAI particles. This result should alleviate concerns of patients on highly active antiretroviral therapy (HAART), that protease inhibitors might accelerate progression of the disease through enhanced production of defective, 'immature'-appearing particles.
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PMID:Fusion of uninfected T-cells occurs with immature HIV-1 protease-mutant, but not morphologically similar protease inhibitor derived particles. 1072 46

Efavirenz (also known as DMP 266 or SUSTIVA) is a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and of HIV-1 replication in vitro and in vivo. Most patients on efavirenz-containing regimens have sustained antiviral responses; however, rebounds in plasma viral load have been observed in some patients in association with the emergence of mutant strains of HIV-1. Virus isolates from the peripheral blood mononuclear cells (PBMCs) of patients with such treatment failures, as well as recombinant viruses incorporating viral sequences derived from patient plasma, show reduced in vitro susceptibility to efavirenz in association with mutations in the RT gene encoding K103N, Y188L, or G190S/E substitutions. Patterns of RT gene mutations and in vitro susceptibility were similar in plasma virus and in viruses isolated from PBMCs. Variant strains of HIV-1 constructed by site-directed mutagenesis confirmed the role of K103N, G190S, and Y188L substitutions in reduced susceptibility to efavirenz. Further, certain secondary mutations (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to efavirenz as single mutations but enhanced the level of resistance of viruses carrying these mutations in combination with K103N or Y188L. Viruses with K103N or Y188L mutations, regardless of the initial selecting nonnucleoside RT inhibitor (NNRTI), exhibited cross-resistance to all of the presently available NNRTIs (efavirenz, nevirapine, and delavirdine). Some virus isolates from nevirapine or delavirdine treatment failures that lacked K103N or Y188L mutations remained susceptible to efavirenz in vitro, although the clinical significance of this finding is presently unclear.
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PMID:Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. 1133 79

DMP 266, a nonnucleoside reverse transcriptase inhibitor, has been effective as a monotherapeutic agent in reducing viral load. How long it remains effective is unknown, and resistance development is a problem. Two trials testing combinations with DMP 266 are beginning. One test using DMP 266 with indinavir is already considered flawed because indinavir is provided as a monotherapy first. Indinavir monotherapy is believed to help HIV resistance to evolve, especially in people with high baseline viral loads. Participants who are on the monotherapy risk not receiving the full benefit from indinavir and other protease inhibitors because they trigger similar resistance mutations.
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PMID:DMP 266: keep the drug but dump the trial? 1136 85

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

Several trials have found that AZT added little benefit when included in two drug regimens. Human tolerance to AZT and HIV's propensity for becoming resistant to AZT are major problems. AZT remains the most prescribed HIV therapy, particularly in combination with 3TC. A popular solution for patients failing or intolerant to AZT or AZT/3TC has been d4T/3TC. AZT is known to penetrate the blood/brain barrier, thus helping to prevent or treat AIDS-related dementia. Over time, however, studies show AZT/3TC and d4T/3TC were essentially equivalent and that both should be helpful for dementia. Another study using d4T/ddI showed reduction in viral loads by 80 to 90 percent at 24 weeks, accompanied by a CD4 rise of about 40, but with significant neurological adverse effects. Combining d4T/ddI with protease inhibitors presents problems, such as a complicated dosing schedule and harsh gastrointestinal side effects. Combining hydroxyurea with d4T/ddI appears to strengthen this combination's effects. One study showed that the combination of ddI and hydroxyurea was unable to prevent the emergence of mutations that confer ddI resistance; however, the mutants were still sensitive to standard doses of ddI in the presence of hydroxyurea. One other conference report presented results of a two-arm trial comparing DuPont Merck's new DMP 266 plus indinavir to indinavir alone for 24 weeks. At trial's end, viral loads were down 2.2 logs (99.4 percent) in the indinavir arm, and CD4 counts, initially averaging 224, were up about 100 cells in both groups. The results achieved with DMP 266/indinavir rival those achieved with indinavir plus AZT/3TC or any two nucleoside analogs. DMP 266 not only is potent, but is taken only once a day.
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PMID:Dethroning AZT. 1136 6

Several new anti-HIV drugs show great promise in future treatments. Nelfinavir, especially effective in combination with AZT and 3TC, is a new protease inhibitor with fewer and milder side effects than other protease inhibitors. GW-1592 is a new nucleoside analogue that appears to be more effective than earlier ones in reducing HIV viral loads with minimal side effects. Other news drugs, GW-141U89, DMP-266, ABT-378, and MKC-442, are entering clinical trials. Scientists are considering converting HIV therapy into a specialty due to the complications, such as resistance, tolerance, and the need for compliance, of using these products.
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PMID:Preparing for the future. 1136 48

DuPont Merck is conducting clinical trials of its new non-nucleoside reverse transcriptase inhibitor, DMP 266, at more than 100 hospitals. The drug is the first anti-HIV medication to be taken only once a day, and it shows significant viral load decreases when taken in combination with indinavir. Side effects include rash, sinusitis, upper respiratory infection, and diarrhea. Enrollment information is included. Merck will announce an expanded access program in September 1997.
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PMID:DMP 266 on the horizon. 1136 36

Results of a 48-week phase II trial of efavirenz (SUSTIVA, formerly DMP 266) in combination with indinavir resulted in an average viral load reduction of 2.38 out of a possible 2.49 logs. A comparison group, receiving only indinavir for 48 weeks, had a 1.89 log average reduction out of a possible 2.42 logs. Efavirenz, produced by DuPont Merck, is a non-nucleoside reverse transcriptase inhibitor that is effective against many HIV variants and resistance also develops slowly. Data from another study on efavirenz will be reported at the Sixth European Conference on Clinical Aspects and Treatment of HIV Infection, October 11-15 in Hamburg, Germany. The additional number that is used to report viral load measurements is explained.
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PMID:Efavirenz (SUSTIVA, formerly DMP-266) 48-week data announced. 1136 90


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