一項新研究顯示,，那些用抗逆轉(zhuǎn)錄病毒療法治療沒有效果的艾滋病病毒感染者，將來再結(jié)合用一種氨基酸藥物進(jìn)行治療,，或許可以顯著改善他們的生存狀態(tài),。
英國帝國理工學(xué)院等機(jī)構(gòu)的研究人員4月1日在《免疫學(xué)雜志》（The Journal of Immunology）上說，他們把一種名為D-1mT的氨基酸藥物與抗逆轉(zhuǎn)錄病毒療法結(jié)合使用,，顯著降低了獼猴體內(nèi)的猿類免疫缺陷病毒SIV的水平,。SIV是迄今已知與人類艾滋病病毒最接近的病毒。
目前,，治療艾滋病通常使用高效抗逆轉(zhuǎn)錄病毒療法,，俗稱雞尾酒療法，但約有十分之一的艾滋病病毒感染者由于抗藥性等因素,，這種療法對他們沒有療效,。因此研究人員希望他們的新研究將來能提高雞尾酒療法的療效。
研究人員在實驗中共使用了11只感染SIV的獼猴,，它們先接受雞尾酒療法,，療程至少4個月,，結(jié)果其中只有3只體內(nèi)的SIV降到不可測的水平，另8只則不見療效,，SIV依然保持較高水平,。
研究人員接著讓這8只獼猴每天服用一定劑量的D-1mT，并在第6天和第13天時接受血液檢測,，結(jié)果發(fā)現(xiàn),，第6天時只剩下3只獼猴體內(nèi)SIV含量仍處于可測水平，第13天時只剩下2只獼猴體內(nèi)SIV含量處于可測水平,，且含量非常低,。
此外，動物實驗還證實,，只使用D-1mT治療感染SIV的獼猴并沒有療效,。研究人員表示，下一步他們將研究D-1mT是如何發(fā)揮功效的,。
目前,，一些研究小組正在進(jìn)行初步臨床試驗驗證D-1mT治療癌癥的安全性和功效。研究人員指出,，如果試驗證明D-1mT能安全運用于人體,，預(yù)計他們最早將于5年內(nèi)開始實施D-1mT治療艾滋病的臨床試驗。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
