Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of reduced doses of Ritonavir (RIT) and Saquinavir (SQV) is considered a potent alternative in treating patients infected by HIV-1. We tested a combination of 300mg of RIT plus 600mg of SQV, twice daily, in association with two reverse transcriptase inhibitors to treat AIDS patients for a period of 6 months. Evaluation of HIV-1 RNA plasma levels, CD4+/CD8+ cell count and biochemical/hematological parameters (liver enzymes, serum electrolytes, creatinin, blood glucose, uric acid, white blood cell count, platelet count, and hemoglobin level) were performed after 30, 90 and 180 days of therapy. Clinical failure and adverse reactions were also recorded in order to assess safety and efficacy of the treatment. A total of 30 AIDS patients (25 male; 5 female) were enrolled in the study. Eight patients discontinued the therapy due to intolerance, 2 patients presented clinical failure (onset of AIDS-defining events during the study period), 2 patients werc excluded due to protocol violation. Five patients tolerated only a lower dose of RIT (400mg/day). Patients who completed 6 months of therapy had a drop in viral load from 4.8+/-.7 log(10) median 4.9 log) to 3.4 +/- 1.0 log(10) (median 2.6 log), and an increase in CD4+ count from 109 +/- 86cells/ml (median 84cells/ml) to 249+/- 114 cells/ml (median 265 cells/ml), compared to baseline values. However, patients who used a lower dose of RIT (400mg/day) had a less impressive drop in viral load values (mean 0.6 log(10) NA copies/ml) when compared with those using the 600mg/day of the drug (mean 2.4 log(10)). The percentage of patients presenting undetectable levels of HIV-1 RNA in plasma was quite different for the 2 groups: 92% of patients with a viral load <400 RNA copies/ ml were using 600mg of RIT. The combination of reduced doses of RIT and SQV reduced viral load >1.0 log(10) after 6 months in 83% of study patients. The dose of 600mg/day of RIT was morc effective in reducing viral load than 400mg/day, but was less well-tolerated. CD4+ cell counts increased in all patients regardless of the RIT dose used.
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PMID:Safety and Efficacy of Reduced Doses of Ritonavir (RTV) Plus Saquinavir (SQV) in the Treatment of AIDS Patients in Brazil. 1109 12

We evaluated the anti-HIV-1 activity of the T-cell-specific protein inhibitor PEG-asparaginase (PEG-ASNase) in human HIV-1-infected T-cells. We further examined the drug synergism between PEG-ASNase and the protease inhibitor Saquinavir (SAQ), both alone and in combination with nucleoside analog reverse transcriptase inhibitors (NRTI). Our drug synergism studies served as a model for an HIV-induced T-cell lymphoma. Phytohemagglutinin [PHA(+)] stimulated T-cells were infected with HIV-1 and then treated with one or more drugs 90 minutes from the viral exposure. To measure inhibition of viral replication, we examined HIV-1 RT and HIV-1 RNA in the supernatant and intracellularly on day 7 post-infection and drug treatment. Last, we examined the effect of administering drugs immediately after HIV-1 infection of T-cells to simulate treatment after an accidental exposure to the virus. PEG-ASNase, even when used alone, has anti-HIV-1 activity in PHA(+)-stimulated T-cells due to inhibition of protein synthesis. When the drug was used with SAQ, the combination was synergistic in inhibiting HIV-1 RT and RNA in the supernatant and intracellularly by 2.5 log10 in comparison with controls. PEG-ASNase and SAQ were even more effective in inhibiting HIV-1 replication when combined with the NRTI inhibitors azidothymidine (AZT) and (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC, lamivudine). The addition of ribonucleotide reductase inhibitor, 2-methyl-1H-isoindole-1,3-dione (MISID), further potentiated the antiviral effect of the regimen. HIV-1 RT and RNA analyses showed that the administration of the PEG-ASNase + SAQ drug combination immediately following exposure to HIV-1 completely inhibited the infection of T-cells in our in vitro T-cell model. From these results we conclude that PEG-ASNase is a valuable T-cell-specific protein inhibitor against HIV-1 infection, when used singly or in combination with a protease inhibitor, an RT inhibitor and an RR inhibitor. Since PEG-ASNase is a drug of choice for the treatment of T-cell lymphomas, a combination regimen containing PEG-ASNase could be very effective in the treatment of HIV-1-induced T-cell lymphoma and possibly AIDS. Future studies are needed in HIV-infected and/or HIV-induced T-cell lymphoma patients to investigate these findings.
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PMID:Synergistic antiviral effect of PEG-asparaginase (ONCASPAR), with protease inhibitor alone and in combination with RT inhibitors against HIV-1 infected T-cells: a model of HIV-1-induced T-cell lymphoma. 1128 17

Saquinavir is a peptidomimetic inhibitor of HIV protease. Initially marketed as Invirasetrade mark, the effectiveness of saquinavir was greatly hindered by its nearly complete first pass metabolism by cytochrome P450 3A4. A new formulation, Fortovasetrade mark, appears to yield some six times the drug exposure and has been demonstrated to yield virological and immunological results similar to those of other protease inhibitors (PIs) when used in conjunction with two nucleoside reverse transcriptase inhibitors (nRTIs). Emerging data suggest it is safe to use twice daily. Co-administration of either formulation of saquinavir with nelfinavir and especially ritonavir yields greatly increased blood levels, with corresponding superior magnitude and durability of viral suppression in first line therapy, albeit with increased adverse effects. The combination of ritonavir and saquinavir has also yielded the most promising results published for second line therapy, after virological breakthrough on previous PI-containing therapy. In addition, preliminary data suggests the possibility of once daily dosing of ritonavir and saquinavir, which would be expected to increase compliance and allow for direct observed therapy.
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PMID:Pharmacology and clinical experience with saquinavir. 1133 88

Saquinavir, a protease inhibitor, received Food and Drug Administration (FDA) approval. Ritonavir and indinavir are likely to receive FDA approval by mid-1996, and three others are currently in clinical trials. Clinicians who treat HIV-positive patients will be faced with conflicting test results and multiple choices in drug therapy. All tests currently show that protease inhibitors are most effective in combination with nucleoside analog reverse transcriptase inhibitors. The issue of cross-resistance is controversial, with differing opinions on whether these treatments reduce the effectiveness of later treatments with other compounds. For the most effective treatment, patients should begin therapy with the maximum tolerated dosage of any of these drugs. A chart summarizes each of the six drugs' developmental statuses. Clinicians are cautioned to consider variables other than viral load in determining which drugs to prescribe; side effects, cost, drug interactions, tissue distribution and palatability are also important factors to consider. Test results of the six drugs are reviewed.
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PMID:The rolling uncertainties of antiprotease prescribing. 1136 41

Several new drugs are under development, and four are expected to reach the U.S. market during 1998. Some of the drugs are variations of existing drugs, such as Fortovase, a soft gel formulation of saquinavir. Several protease inhibitors and non-nucleoside reverse transcriptase inhibitors are also being developed and tested. Questions remain about how effectively the drugs work in combination with each other, which combinations are least likely to lead to resistance and HIV mutation, and which may have potentially serious side effects associated with their use. There is concern with some of these new drugs that resistance to earlier drugs may have a cumulative effect, lessening the effectiveness of the medications.
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PMID:The medical merry-go-round: drugs for 1998 are new but not novel. 1136 84

During the past two years, two new classes of drugs have emerged that are effective in treating HIV infection. Since protease inhibitors and non-nucleoside reverse transcriptase inhibitors are highly effective but difficult to take, pharmaceutical manufacturers have developed new formulations of some of these drugs. People taking AZT and ritonavir can sometimes switch to a product called Combivir, a combination of the two. Saquinavir patients may be able to switch to a gel formulation of the same drug, Fortovase, that is more readily absorbed by the body. Potential side effects and impacts on treatment are reviewed.
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PMID:New ways to take old drugs. 1136 12

Most patients on protease inhibitors who plateau at viral loads within quantifiable levels must switch to an alternative or salvage therapy to continue to decrease these loads and maintain some form of antiviral therapy. The Public Health Service Guidelines suggest using a different therapy if a particular therapy does not substantially lower viral loads to below quantifiable levels within four to six months. Physicians and researchers at the International Workshop on Salvage Therapy for HIV Infection advocated progressively switching patients to a more suppressive regimen to give them a better chance of long-term success. However, if a patient has a stable viral load or there is only a short-term benefit from switching early in therapy, then using a salvage therapy may not be warranted. Results from salvage therapies used for saquinavir failures are mixed. As with nelfinavir, subsequent regimens for patients failing indinavir have a better chance of success when implemented early in treatment. Saquinavir and nelfinavir combined seem to get better results when administered with two reverse transcriptase inhibitors. Use of new experimental drugs as a secondary therapy have mainly short-term benefits and conflicting side effects. Dr. Keith Henry of Regions Hospital in St. Paul treats each case individually. Dr. Henry cautions not to aim for short-term responses and avoid using alternative treatments too quickly, leaving little recourse after viral rebound. Further clinical trials are underway and more are planned to test additional salvage protocols.
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PMID:The great salvage therapy drug juggle. 1136 98

Antiviral drugs, like any trend, may be in demand one year but passe the next. Saquinavir is an example of this trendiness. Initially, it was in great demand, but within 2 years the side effects had reduced the demand. Efavirenz (Sustiva), a non-nucleoside reverse transcriptase inhibitor, is the new trend. The Geneva Conference provided study results showing that a regimen containing efavirenz plus AZT plus 3TC helped 95 percent of the patients reduce their viral load to below detectable levels after 24 weeks of therapy. Efavirenz also requires only one dose per day, and it can be taken with or without food.
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PMID:Dressing up your virus: a new outfit for HIV. 1136 10

Availability of clinical data on HIV and women is limited, yet women constitute the fastest growing population with HIV infection. Hoffman LaRoche has announced a study that will examine the different responses of men and women to anti-HIV therapy. The study will compare responses to the protease inhibitor Fortovase (Saquinavir soft-gel capsules) combined with two nucleoside reverse transcriptase inhibitors. Enrollment information and studies details are included.
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PMID:Are men and women really different? 1136 80

Four protease inhibitors are compared: Saquinavir (Invirase, Fortovase), Indinavir (Crixivan), Ritonavir (Norvir), and Nelfinavir (Viracept). Key questions are answered on how dosages change when combined with nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and other protease inhibitors. Information on administration and storage and the impact of each drug on disease development are reviewed. Drug interactions between protease inhibitors and other HIV drugs and non-HIV medications are described. Side effects are also discussed. Pediatric use is addressed, including suggested dosages. Contact information for each manufacturer is provided, along with approximate annual price for treatment.
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PMID:Protease inhibitors at a glance.... 1136 98


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