Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While it appears that protease inhibitors in combination therapies are saving lives, questions continue: (1) which combinations of protease inhibitors and other antiretroviral agents are most effective in restoring immune function, (2) how these combinations can be used most effectively, and (3) what is the best time to start using them? An evaluation is presented on the immunological value of specific drug cocktail combinations and a comparison of the best and worst drug combinations and the reasons for this assessment. It indicates that Norvir is the most effective of all four protease inhibitors in preventing opportunistic infections, lymphomas, and cancers. D4T and 3TC are the safest and most effective of the nucleosides for preventing or remitting opportunistic infections when used with protease inhibitors. Rescriptor is the most therapeutic of the two non-nucleoside reverse transcriptase inhibitors in increasing absorption of protease inhibitors. The best drug combination therapies are listed as follows: Norvir plus Rescriptor; Norvir plus D4T; Norvir plus 3TC; Norvir, Rescriptor, and D4T; Norvir, Rescriptor, and 3TC; Norvir, D4T, and 3TC; and Crixivan or Viracept plus Rescriptor plus either D4T or 3TC. The worst drug combination therapies are listed as follows: AZT plus ddI (used in combination with a protease inhibitor); AZT or ddI or Combivir (used in combinations with a protease inhibitor); and any two protease inhibitors used together in any person with active hepatitis or elevated liver enzymes or impaired kidney function.
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PMID:An evaluation of drug cocktail combinations for their immunological value in preventing/remitting opportunistic infections. 1136 16

Recent progress in treatment methods and medicines has made HIV more manageable. Factors contributing to this progress include advances in testing; the use and approval of protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and other nucleosides; and the success of highly active antiretroviral regimens (HAART) and combination therapy. Nucleoside reverse transcriptase inhibitors, such as Zidovudine and Didanosine, and non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as Nevirapine (Viramune) and Delavirdine (Rescriptor), are recommended for use in combination therapy. The pharmacology, side effects, and contraindications of these types of drugs are provided. Dosages and common side effects are also mentioned.
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PMID:Understanding the reverse transcriptase inhibitors in HIV. 1136 42

It was previously found that certain nonnucleoside reverse transcriptase inhibitors (NNRTI) possess virucidal activity against human immunodeficiency virus type 1 (HIV-1), and it was suggested that the tight-binding mode of inhibition of reverse transcriptase might be important for this virucidal activity (Borkow et al., J. Virol. 71:3023-3030, 1997). To test this, we compared six different NNRTI, including three tight-binding NNRTI, namely UC781, efavirenz (EFV) (Sustiva), and 5-chloro-3-phenylsulfonylindole-2-carboxamide (CSIC), and three rapid-equilibrium NNRTI, delavirdine (DLV) (Rescriptor), nevirapine (NVP) (Viramune), and UC84, in a variety of virucidal tests. Incubation of isolated HIV-1 virions with UC781, EFV, or CSIC rapidly inactivated the virus, whereas DLV, NVP, and UC84 were ineffective in this respect. Exposure of H9+ cells chronically infected by HIV-1 to the tight-binding NNRTI abolished the infectivity of nascent virus subsequently produced by these cells following removal of extracellular drug, thereby preventing cell-to-cell virus transmission in the absence of exogenous drug. In contrast, cell-to-cell transmission of HIV was blocked by DLV, NVP, and UC84 only when the drug remained in the extracellular medium. Pretreatment of uninfected lymphocytoid cells with UC781, EFV, or CSIC, but not DLV, NVP, or UC84, protected these cells from subsequent HIV-1 infection in the absence of extracellular drug. The protective effect was dependent on both the dose of NNRTI and the viral load. The overall virucidal efficacy of the tight-binding NNRTI tested was CSIC > UC781 approximately EFV. We conclude that the tight-binding mode of inhibition is an essential characteristic for virucidal NNRTI and that antiviral potency is an insufficient predictor for virucidal utility of NNRTI.
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PMID:A tight-binding mode of inhibition is essential for anti-human immunodeficiency virus type 1 virucidal activity of nonnucleoside reverse transcriptase inhibitors. 1201


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