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)

Chimpanzees were challenged with HIV-1IIIB while receiving a short regimen of nevirapine (Viramune), a nonnucleoside inhibitor of HIV-1 reverse transcriptase. The untreated, control chimpanzee developed an infection characterized by seroconversion, viremia in peripheral blood mononuclear cells (PBMCs), and plasma positive for viral RNA. In contrast, the three nevirapine-treated chimpanzees remained negative for all viral markers with the exception of nested polymerase chain reaction (PCR) analysis of PBMCs for viral DNA. Although PBMCs from the three nevirapine-treated chimpanzees tested intermittently positive for viral DNA, this PCR signal disappeared and remained negative for the final five months of the study. These data indicate that orally administered nevirapine provided protection from HIV-1 infection in the chimpanzee model.
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PMID:Prophylaxis against HIV-1 infection in chimpanzees by nevirapine, a nonnucleoside inhibitor of reverse transcriptase. 917 94

Modification of the non-nucleoside inhibitor of HIV-1 reverse transcriptase nevirapine (Viramune) by incorporation of a 2-indolyl substituent confers activity against several mutant forms of the enzyme.
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PMID:Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. 6. 2-Indol-3-yl- and 2-azaindol-3-yl-dipyridodiazepinones. 924 Mar 58

Like other nonnucleoside inhibitors of HIV-1 reverse transcriptase, the dipyridodiazepinone nevirapine (Viramune, 1) selects for drug resistant variants of HIV-1, both in cell culture and in patients. In particular, the mutation of residue 181 from tyrosine to cysteine (Y181C) is associated with resistance to most reported nonnucleoside inhibitors. Introduction of an arylethyl substituent at the 8-position of the tricyclic dipyridodiazepinone skeleton confers enhanced potency against Y181C RT. Several analogues of this series display good broad spectrum potency against a panel of mutant enzymes.
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PMID:Novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 7. 8-Arylethyldipyridodiazepinones as potent broad-spectrum inhibitors of wild-type and mutant enzymes. 968 35

3-(5-Dimethylamino-1-naphthalenesulphonyl)-2-(3-pyridyl)thiazolidi ne (YHI-1), a synthetic analogue of D-cysteinolic acid isolated from sardines (Sardinops melanostictus), was found to be a specific inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in various cell cultures. YHI-1 inhibited HIV-1IIIB replication with a 50% effective concentration (EC50) of 3.35, 10.23 and 4.61 microM in MT-4 cells, peripheral blood mononuclear cells and MAGI-CCR5 cells, respectively. However, no antiviral activity was observed with non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 strains, such as nevirapine-resistant HIV-1HE/NEV and MKC-442-resistant HIV-1IIIB-R, or with HIV-2ROD or SIVMAC. YHI-1 failed to inhibit reverse transcriptase (RT) activity in vitro with different template-primer systems. Time-of-addition experiments, the failure to inhibit NNRTI-resistant strains and the failure to show in vitro activity against RT suggest that a metabolite of YHI-1 inside the cell acts like an NNRTI. Thus, YHI-1 seems to belong to a new class of HIV-1 inhibitor and is a good candidate for further development.
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PMID:3-(5-Dimethylamino-1-naphthalenesulphonyl)-2-(3-pyridyl)thiazolidine (YHI-1) selectively inhibits human immunodeficiency virus type 1. 987 95

Phenotypic drug susceptibility assays of human immunodeficiency virus type 1 (HIV-1) isolates generally use time-consuming, expensive assays with peripheral blood mononuclear cells. A new HIV-1 indicator cell line, MAGI-CCR5, has been developed and applied for this purpose. This cell line expresses human CD4, the two major HIV-1 coreceptors, CCR5 and CXCR4, the reporter gene beta-galactosidase driven by the HIV-1 LTR, and quantitates infection within 48 h. A panel of reference strains and primary HIV-1 isolates were all found to infect this cell line. Susceptibility assays with a nucleoside (zidovudine, ZDV) and a non-nucleoside reverse transcriptase inhibitor (nevirapine, NVP) were performed with reference and primary isolates. The assay was modified into two steps for protease inhibitor (indivinavir, IDV and ritonavir, RTV) susceptibility assays. Primary isolates derived from drug naive patients displayed mean baseline 50% effective concentrations (EC50) of 0.14 microM for ZDV, 0.33 microM for NVP, and 0.02 microM for IDV. Isolates derived from patients under treatment displayed increased EC50 concentrations. The MAGI-CCR5 cell line offers a rapid, efficient, and reproducible method of testing a wide range of HIV-1 isolates for drug susceptibility.
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PMID:Rapid phenotypic drug susceptibility assay for HIV-1 with a CCR5 expressing indicator cell line. 1071 48

Nevirapine (Viramune), a dipyridiodiazepinone, is a potent and highly specific nonnucleoside inhibitor of HIV-1 reverse transcriptase. This paper describes the validation of a specific, sensitive, and stability-indicating high-performance liquid chromatography method for the assay and determination of related organic impurities in nevirapine drug substance. This method uses a Supelcosil LC-ABZ column, a mobile phase of 20:80 (v/v) acetonitrile-25mM NH4H2PO4 (pH 5.0), and ultraviolet detection at a wavelength of 220 nm. This method was validated for specificity, linearity, accuracy, repeatability, detection limit, quantitation limit, stability of analyte solutions, robustness, and intermediate precision. Nevirapine is completely separated from all impurities. The method is shown to be linear with coefficients of determination r2 greater than 0.999. Average accuracy is 100.4% with a relative standard deviation of 0.7% for the assay. Accuracy ranges from 100.1 to 102.6% for related organic impurities. Repeatability is good, with relative standard deviations not more than 1.4%. The detection limit and the quantitation limit are determined to be 0.001 and 0.003%, respectively. Relative response factors of known organic impurities are determined, permitting the use of nevirapine at the 0.1% level as an external standard for the quantitation of these impurities. Analyte solutions are shown to be stable for at least 2 days at ambient temperature. The method is validated as robust, and intermediate precision is high. A system suitability test is developed and validated, and requirements are set.
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PMID:Validation of a high-performance liquid chromatography method for the assay of and determination of related organic impurities in nevirapine drug substance. 1089 Jul 48

Boehringer-Ingelheim Pharmaceuticals is offering an expanded access program for its non-nucleoside reverse transcriptase inhibitor, nevirapine (Viramune). Criteria for inclusion are that participants be at least 13 years old, with a CD4 count below 50, and be intolerant to currently approved HIV treatments. The company expects to file an application for accelerated approval of nevirapine with the Food and Drug Administration (FDA) by March 1996.
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PMID:Nevirapine expanded access. 1136 63

An antiviral drugs advisory committee unanimously recommended accelerated approval for nevirapine (Viramune) for combination therapy with other anti-HIV drugs. Nevirapine, produced by Boehringer Ingelheim Parmaceuticals, is the first non-nucleoside reverse transcriptase inhibitor (NNRTI) to be approved by the Food and Drug Administration (FDA). Studies have shown that best results were seen when patients started using the drug at the same time they began using previously untried nucleoside analogs. In April, an expanded access program was initiated to make Viramune available to adult and pediatric patients with progressive, symptomatic disease.
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PMID:Nevirapine recommended for approval. 1136 50

The U.S. Food and Drug Administration (FDA) recently approved nevirapine (Viramune), a non-nucleoside reverse transcriptase inhibitor. This is the first approval for a new class of drugs that uses a different mechanism to stop HIV from replicating. The approval was based on several recent studies showing that nevirapine has a strong and lasting antiretroviral effect when used with combination therapy. However, earlier studies with nevirapine alone or in combination with one drug were not promising because of the rapid development of drug resistance. Boehringer Ingelheim Pharmaceuticals of Indianapolis took over the testing of the drug from Merck & Co. of Rahway, NJ. When nevirapine was combined with zidovudine (AZT) and didanosine (ddI), patients' CD4 counts rose significantly and viral load was reduced to below detectable levels. Although the results are impressive, more than 20 percent of the patients dropped out of the study, primarily because of the side effects. Some clinicians are wary of using the drug because of toxicity, since no survival or clinical data are available.
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PMID:FDA approves first new class of HIV drugs. Food and Drug Administration. 1136 55

The Food and Drug Administration (FDA) granted accelerated approval to nevirapine (Viramune) on June 24, 1996. Nevirapine is the first of another new class of anti-HIV drugs, non-nucleoside reverse transcriptase inhibitors, to receive approval. Studies have shown viral load drops of 95 percent or more, but the participants in the study were limited to those who had never used antiretroviral therapy before. The drug must be taken in combination with nucleoside analogues, as resistance to nevirapine monotherapy develops in two weeks.
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PMID:Nevirapine approval expands combo possibilities--and HIV suppression. 1136 91


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