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)

An advisory committee of the Food and Drug Administration (FDA) has recommended accelerated approval for abacavir (ABC, Ziagen). The approval decision was not unanimous due to concerns of drug toxicity. Three percent of those taking the drug have developed severe allergic reactions, and at least eight people have died of complications related to the allergic reaction. Abacavir works by attacking the viral enzyme reverse transcriptase (RT), and it is related to other drugs such as AZT, 3TC, d4T, ddI, and ddC. Abacavir should be taken twice daily, in combination with other anti-HIV medications.
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PMID:Abacavir gets green light from FDA advisory board. Food and Drug Administration. 1136 24

The experimental reverse transcriptase inhibitor FddA (lodenosine) has shown promise in early studies. The drug was originally developed by the National Cancer Institute (NCI) and appears to have little in vitro cross-resistance with other drugs in its class, including AZT (Retrovir), ddI (Videx), and d4T (Zerit). Drug trials are in the early stages, and there is limited data on the drug to date. The NCI is planning a Phase I/II trial. U.S. Bioscience is planning a Phase II trial to study FddA in combination with a protease inhibitor plus a nucleoside analog in treatment-naive patients. Contact information is provided.
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PMID:FddA: antiretroviral in development. 1136 97

The First International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV took place in June 1999. Speakers discussed various theories on the causes of lipodystrophy, including mitochondrial toxicities. Factors including gender, age, and disease stage seem to affect the risk of developing lipodystrophy, or fat redistribution syndrome. Some studies are investigating the relationship between lipodystrophy and HIV drugs, such as the use of d4T, a nucleoside analog reverse transcriptase inhibitor (NRTI). Contact information is provided.
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PMID:Drug reactions & lipodystrophy workshop. 1136 65

Several research teams attended the 1st International Workshop on Adverse Drug Reactions and Liposdystrophy in HIV. Under discussion were the effects of reverse transcriptase (RT) inhibitors and nucleoside RT inhibitors (NRTIs) on lipodystrophy, also known as fat redistribution. Key findings included correlating lipodystrophy with long-term treatment by RTs, linking fat redistribution to Stavudine (d4T), and determining effects of various protease inhibitors which contribute to lipodystrophy. Results from an Italian study showed women were more likely than men to have fat abnormalities. An Australian research team presented a cohort study detailing risk factors for lipodystrophy. Harmful consequences of lipodystrophy were reviewed, such as increased cardiac risk due to elevated plasma triglycerides and cholesterol, and increased incidence of diabetes. The drawbacks of antiretroviral treatment tactics were also discussed. In addition, lipodystrophy treatments include aerobics and resistance training, injections of recombinant human growth hormone, and lipid-lowering drugs.
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PMID:On the trail of fugitive fat: the chase turns to NRTIs. 1136 71

A study of Triangle Pharmaceuticals' non-nucleoside reverse transcriptase inhibitor, Coactinon, found that the drug significantly suppressed viral replication when used with d4T and 3TC. The manufacturer reported mild side effects, including nausea, headache, dizziness, diarrhea, and rash.
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PMID:Triangle Pharma Coactinon combo may suppress HIV. 1136 23

Hydroxyurea (Hydrea) is an antiviral drug approved for use against cancer and sickle cell anemia. Produced by Bristol-Myers Squibb, it has not yet received Food and Drug Administration (FDA) approval for use against HIV; however, trial results are promising. The drug works by blocking a human cell enzyme used to multiply cells, and appears to be most effective when combined with reverse transcriptase inhibitors such as ddI or d4T. HIV does not develop resistance to hydroxyurea, and hydroxyurea can slow mutations in the virus. It is taken once or twice daily and is available in 500 mg tablets.
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PMID:Hydroxyurea: what it is. New Mexico AIDS InfoNet. 1136 49

We have found a close correlation between viral stavudine (d4T) resistance and resistance to d4T-triphosphate at the human immunodeficiency virus type 1 reverse transcriptase (RT) level. RT from site-directed mutants with 69S-XX codon insertions and/or conventional zidovudine resistance mutations seems to be involved in an ATP-dependent resistance mechanism analogous to pyrophosphorolysis, whereas the mechanism for RT with the Q151M or V75T mutation appears to be independent of added ATP for reducing binding to d4T-triphosphate.
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PMID:Biochemical mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to stavudine. 1140 40

We studied the intrahost evolution and dynamics of a multidrug-resistant HIV-1, which contains an insertion of two amino acids (aa) and several aa changes within the reverse transcriptase (RT) gene. From an individual receiving intermittent therapy, sequences of 231 full-length molecular clones of HIV-1 RT were obtained from serum-derived viruses at 12 consecutive time points over a period of 6 years, 17 to 20 clones per time point. In the 3.5-year period prior to the first course of therapy, only wild-type (wt) viruses were found. As soon as 6 months after the start of zidovudine (AZT) monotherapy, all viruses contained an insertion of two aa between positions 68 and 69 of the RT and aa changes at positions 67 and 215, a combination conferring resistance to multiple nucleoside analogs. After termination of therapy, the insertion mutants were rapidly and completely replaced by the wt viruses. In turn, the insertion mutants replaced the wt viruses after initiation of therapy with 3TC, d4T, and saquinavir. After termination of triple therapy, the wt viruses completely replaced the mutants within 1 month, which is markedly faster than has been observed earlier for the replacement of AZT-resistant viruses. Fast replacements of the mutant virus populations after termination of therapy indicate gross competitive disadvantage of the insertion mutant in the absence of therapy, which we estimated by using several models. The insertion mutants attained high virus loads, demonstrating that virus load cannot be used as a direct measure of virus fitness.
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PMID:Selection by AZT and rapid replacement in the absence of drugs of HIV type 1 resistant to multiple nucleoside analogs. 1142 22

Human foamy virus (HFV), a retrovirus of simian origin which occasionally infects humans, is the basis of retroviral vectors in development for gene therapy. Clinical considerations of how to treat patients developing an uncontrolled infection by either HFV or HFV-based vectors need to be raised. We determined the susceptibility of the HFV to dideoxynucleosides and found that only zidovudine was equally efficient against the replication of human immunodeficiency virus type 1 (HIV-1) and HFV. By contrast, zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), and didanosine (ddI) were 3-, 3-, 30-, and 46-fold less efficient against HFV than against HIV-1, respectively. Some amino acid residues known to be involved in HIV-1 resistance to ddC, 3TC, d4T, and ddI were found at homologous positions of HFV reverse transcriptase (RT). These critical amino acids are located at the same positions in the three-dimensional structure of HIV-1 and HFV RT, suggesting that both enzymes share common patterns of inhibition.
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PMID:Efficacy of dideoxynucleosides against human foamy virus and relationship to its reverse transcriptase amino acid sequence and structure. 1143 99

Prior evidence suggests that resistance to zidovudine (ZDV) confers some degree of cross-resistance to stavudine (d4T), but no genotypic correlates of clinical d4T susceptibility and resistance exist. To identify the genotypic correlates of a virologic response to d4T, reverse transcriptase (RT) sequencing of archived plasma HIV isolates was performed on 31 subjects who received d4T monotherapy in the AIDS Clinical Trials Group 302 study, all of whom received more than 3 years of ZDV monotherapy. Baseline characteristics and all RT mutations were analyzed for impact on virologic suppression. Eight of 31 subjects (27%) achieved a virologic response of greater than 0.3 log reduction in plasma HIV RNA after 8 weeks of d4T. Responders were more likely to have lower median baseline viral loads (4.2 vs. 4.7; p =.01) and a trend toward fewer ZDV-associated mutations (median: 1 vs. 2; p =.09). No subject with greater than one ZDV mutation had a virologic response to d4T. Seven of the 8 responders had only a K70R mutation at baseline. We conclude that in patients with prior ZDV treatment, those with only one ZDV mutation, particularly at position 70, can still get reasonable virologic activity from d4T. Those with more mutations are not likely to have much benefit.
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PMID:Genotypic correlates of a virologic response to stavudine after zidovudine monotherapy. 1146 26


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