一项新研究显示，那些用抗逆转录病毒疗法治疗没有效果的艾滋病病毒感染者，将来再结合用一种氨基酸药物进行治疗，或许可以显著改善他们的生存状态。
英国帝国理工学院等机构的研究人员4月1日在《免疫学杂志》（The Journal of Immunology）上说，他们把一种名为D-1mT的氨基酸药物与抗逆转录病毒疗法结合使用，显著降低了猕猴体内的猿类免疫缺陷病毒SIV的水平。SIV是迄今已知与人类艾滋病病毒最接近的病毒。
目前，治疗艾滋病通常使用高效抗逆转录病毒疗法，俗称鸡尾酒疗法，但约有十分之一的艾滋病病毒感染者由于抗药性等因素，这种疗法对他们没有疗效。因此研究人员希望他们的新研究将来能提高鸡尾酒疗法的疗效。
研究人员在实验中共使用了11只感染SIV的猕猴，它们先接受鸡尾酒疗法，疗程至少4个月，结果其中只有3只体内的SIV降到不可测的水平，另8只则不见疗效，SIV依然保持较高水平。
研究人员接着让这8只猕猴每天服用一定剂量的D-1mT，并在第6天和第13天时接受血液检测，结果发现，第6天时只剩下3只猕猴体内SIV含量仍处于可测水平，第13天时只剩下2只猕猴体内SIV含量处于可测水平，且含量非常低。
此外，动物实验还证实，只使用D-1mT治疗感染SIV的猕猴并没有疗效。研究人员表示，下一步他们将研究D-1mT是如何发挥功效的。
目前，一些研究小组正在进行初步临床试验验证D-1mT治疗癌症的安全性和功效。研究人员指出，如果试验证明D-1mT能安全运用于人体，预计他们最早将于5年内开始实施D-1mT治疗艾滋病的临床试验。（生物谷Bioon.com）
生物谷推荐原始出处：
The Journal of Immunology, 2009, 182: 4313-4320
Combined Effect of Antiretroviral Therapy and Blockade of IDO in SIV-Infected Rhesus Macaques1
Adriano Boasso2,3,*,, Monica Vaccari2,, Dietmar Fuchs, Andrew W. Hardy4,*, Wen-Po Tsai, Elzbieta Tryniszewska5,, Gene M. Shearer* and Genoveffa Franchini
* Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Immunology Department, Imperial College, Chelsea and Westminster Hospital, London, U.K.; Animal Models and Retroviral Vaccines Section, National Cancer Institute, National Institutes of Health, Bethesda MD 20892; and Division of Biological Chemistry Biocentre, Innsbruck Medical University, Innsbruck, Austria
Increased activity of IDO, which catalyzes the degradation of Trp into kynurenine (Kyn), is observed during HIV/SIV infection, and it may contribute to the persistence of HIV/SIV by suppressing antiviral T cell responses. We administered the IDO inhibitor 1-methyl-D-tryptophan (D-1mT) for 13 days to SIV-infected rhesus macaques receiving antiretroviral therapy (ART). D-1mT treatment increased the plasma levels of Trp, without reducing the levels of Kyn, suggesting only a partial effect on IDO enzymatic activity. Surprisingly, D-1mT significantly reduced the virus levels in plasma and lymph nodes of ART-treated animals with incomplete responsiveness to ART. In SIV-infected animals that were not receiving ART, D-1mT was ineffective in reducing the plasma viral load and had only a marginal effect on the plasma Kyn/Trp ratio. Increased IDO and TGF-β mRNA expression in lymph nodes of ART-treated macaques after D-1mT treatment suggested that compensatory counterregulatory mechanisms were activated by D-1mT, which may account for the lack of effect on plasma Kyn. Finally, D-1mT did not interfere with the ART-induced T cell dynamics in lymph nodes (increased frequency of total CD4 T cells, increase of CD8 T cells expressing the antiapoptotic molecule Bcl2, and reduction of regulatory T cells). Thus, D-1mT appeared to synergize with ART in inhibiting viral replication and did not interfere with the beneficial immunologic effects of ART. Further studies are required to elucidate the immunologic or virologic mechanism by which D-1mT inhibited SIV replication in vivo.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (to A.B., M.V., A.W.D., W.P.T., E.T., G.M.S., and G.F.), and by the government of the State of the Austrian Tyrol (to D.F.).
2 A.B. and M.V. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Adriano Boasso, Imperial College, Faculty of Medicine, Department of Immunology, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, U.K.
4 Current address: Vitae Pharmaceuticals, Ft. Washington, PA 19034.
5 Current address: Department of Microbiology Diagnostics, Medical University of Bialystok, Bialystok, Poland.
6 Abbreviations used in this paper: ART, antiretroviral therapy; D-1mT, 1-methyl-D-tryptophan; Kyn, kynurenine; Neo, neopterin; Treg, regulatory T cell.
7 The online version of this article contains supplemental material.
