在淋巴细胞和巨噬细胞培养物中,用于治疗hiv -1感染患者的消耗性疾病的奥雄龙不会降低脱氧核苷类似物的抗病毒活性。

D M Segal, M Perez, P Shapshak
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引用次数: 8

摘要

抗病毒药物是HIV-1感染患者的主要治疗方法。然而,由于与HIV-1感染和艾滋病相关的破坏性消耗过程,除了抗病毒药物之外,支持性治疗通常是必要的。奥雄龙是一种合成代谢类固醇,用于促进HIV-1患者体重增加,最重要的是瘦体重(LBM)。我们研究了氧雄龙是否会干扰齐多夫定(ZDV)、二脱氧肌苷(ddI)和二脱氧胞苷(ddC)在外周血淋巴细胞和巨噬细胞中对HIV-1复制的抗病毒活性。核苷类似物在外周淋巴细胞中具有纳摩尔50%的抑制浓度(IC50)。核苷类似物和奥雄龙的组合没有导致IC50值的增加。单独使用奥雄龙在外周血淋巴细胞中显示出微摩尔IC50值。在几种药物、病毒株、外周淋巴细胞和巨噬细胞的组合中,核苷浓度高达5微米和氧雄龙浓度高达100微米时,缺乏干扰是一致的。我们得出结论,奥胺龙可用于促进艾滋病相关消瘦患者的体重增加,而不会干扰ZDV、ddI或ddC的抗病毒作用。
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Oxandrolone, used for treatment of wasting disease in HIV-1-infected patients, does not diminish the antiviral activity of deoxynucleoside analogues in lymphocyte and macrophage cell cultures.

Antiviral agents are the primary therapy for patients infected with HIV-1. However, supportive therapies are often necessary in addition to antiviral drugs because of the devastating wasting process associated with HIV-1 infection and AIDS. Oxandrolone, an anabolic steroid, is used in promoting weight gain and, most important lean body mass (LBM), in patients with HIV-1 disease. We investigated whether oxandrolone interferes with the antiviral activity of zidovudine (ZDV), dideoxyinosine (ddI), and dideoxycytidine (ddC) on HIV-1 replication in peripheral blood lymphocytes and macrophage-monocytes. The nucleoside analogues had nanomolar 50% inhibitory concentrations (IC50) in peripheral lymphocytes. Combinations of nucleoside analogues and oxandrolone did not result in increased IC50 values. Oxandrolone used alone exhibited micromolar IC50 values in peripheral blood lymphocytes. Lack of interference was consistent for nucleoside concentrations up to 5 microM and for oxandrolone concentrations up to 100 microM in several combinations of drugs, viral strains, and peripheral lymphocytes and macrophages. We conclude that oxandrolone can be used for the promotion of weight gain in patients with AIDS-related wasting without interference with the antiviral effects of ZDV, ddI, or ddC.

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