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Drug resistance patterns and their correlation to treatment response 24 weeks after addition of lamivudine to a previous zidovudine/zalcitabine or zidovudine/ didanosine combination treatment, or after substitution of lamivudine for the zalcitabine or didanosine in these combinations, were evaluated in 21 patients with CD4 counts between 50 and 300 cells/mm 3 . Clinical, immunological and virological outcomes were measured at baseline and at weeks 4, 12 and 24. Drug resistance was assessed using the recombinant virus assay and direct solid-phase sequencing of the reverse transcriptase gene. Viral load decreased by an average of 0.78 log RNA copies/ml at week 4, but returned to baseline at week 24 for most patients. CD4 cell counts increased in all treatment groups without reaching statistical significance. Resistance to lamivudine was readily acquired in all four treatment groups and was often associated with a partial reversal of phenotypic zidovudine resistance and a moderate increase in the 50% inhibitory concentrations for didanosine and zalcitabine. One patient receiving the zidovudine/didanosine combination treatment harboured multi-nucleoside analogue-resistant virus. A poor response to lamivudine tended to be related to the extent of pre-existing zidovudine resistance.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

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Abstract Six neutral metallocenes and six metallocenium salts, all of which have demonstrated antiproliferative properties, were evaluated for their in vitro broad‐spectrum antiviral properties and cytotoxicities. The metallocenes include the compounds (η‐C 5 H 5 ) 2 MCl 2 , Where MTi, V, Mo, Zr and Hf, and (η‐C 5 H 5 ) 2 Tibis(hydrogen maleinate), whereas the metallocenium complexes include the three ferrocenium salts, (η‐C 5 H 5 ) 2 Fe + X − , where X − = trichloroacetate, tetrachloroferrate(III) and picrate, and three recently discovered antitumor titanocenium complexes, i.e. [(η‐C 5 H 5 ) 2 Ti(CH 3 CN)Cl + ] [FeCl ], [(η‐C 5 H 5 ) 2 Ti(2,2′‐bipyridyl) 2+ ][CF 3 SO ] 2 , and [(η‐C 5 H 5 ) 2 Ti( N ‐methyl‐ o ‐aminothiophenolate + )] [I − ]. These 12 species were evaluated against DNA viruses (herpes simplex virus type 1, type 2 and vaccinia virus), and RNA viruses [vesicular stomatitis virus, Coxsackie virus B4, Sindbis virus, Semliki forest virus, parainfluenza virus type 3 and human immunodeficiency virus type 1 (HIV‐1), the etiologic agent of AIDS]. In the case of HIV‐1, the complexes were evaluated for their ability to inhibit HIV‐associated reverse transcriptase activity and HIV‐1 induced cytopathogenicity in human T‐lymphocyte MT4 cells. Selectivity indexes [ratio of the minimum cytotoxic concentration (does) to the minimum (antiviral) inhibitory concentration (dose)] were determined for all complexes and viruses. In general, the netural metallocenes and the ferrocenium salts were only marginally active towards some specific viruses. However,[(η‐C 5 H 5 ) 2 Ti(bipy) ] [CF 3 SO ] 2 was active towards the DNA viruses at a concentration that was ten times lower than the cytotoxicity threshold. (η‐C 5 H 5 ) 2 VCL 2 was weakly inhibitory towards HIV reverse transcriptase. All species were ineffective in inhibiting HIV‐induced cytopathogenicity in human T‐lymphocyte MT4 cells.

The synthesis of 5-heteroaryl-substituted 2'-deoxyuridines is described. The heteroaromatics were obtained from three different 5-substituted 2'-deoxyuridines. Cycloaddition reaction of nitrile oxides on the 5-ethynyl derivative 1 gave the isoxazoles 4a-e. The thiazole derivatives 14a-c were obtained from the 5-thiocarboxamide 11, while 5-pyrrol-1-yl-2'-deoxyuridine (17) could be synthesized directly from 5-amino-2'-deoxyuridine. The compounds were evaluated for antiviral activity. Selective activity against herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) was noted for 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridine (4c). The compound was inactive against herpes simplex virus type 2, cytomegalovirus, and thymidine kinase (TK)-deficient mutants of HSV-1 and VZV, which indicates that, most likely, its antiviral activity depends on phosphorylation by the virus-specified TK.