Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.
Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.
复制标题
DOI：
10.1038/nature11286
复制
发表时间：
2012-07-25
期刊：
影响因子：
64.8
通讯作者：
Margolis, D. M.
中科院分区：
文献类型：
--
作者：
Archin, N. M.;Liberty, A. L.;Kashuba, A. D.;Choudhary, S. K.;Kuruc, J. D.;Crooks, A. M.;Parker, D. C.;Anderson, E. M.;Kearney, M. F.;Strain, M. C.;Richman, D. D.;Hudgens, M. G.;Bosch, R. J.;Coffin, J. M.;Eron, J. J.;Hazuda, D. J.;Margolis, D. M.
Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4+ T cells is the primary strategy to clear this reservoir. While histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA or vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Therefore we isolated the circulating resting CD4+ T cells of patients in whom viremia was fully suppressed by antiretroviral therapy (ART), and directly studied the effect of VOR in this latent reservoir. In each of eight patients studied, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4+ cells (mean increase 4.8-fold). This is the first demonstration that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in man, provides proof-of-concept for HDAC inhibitors as a new therapeutic class, and defines a precise approach to test novel strategies to directly attack and eradicate latent HIV infection.
登录
查看更多内容
DOI：
10.1097/qad.0b013e32832ec1dc
发表时间：
2009-09-10
期刊：
AIDS (London, England)
影响因子：
--
作者：
Archin NM;Keedy KS;Espeseth A;Dang H;Hazuda DJ;Margolis DM
通讯作者：
Margolis DM
影响因子：
3.7
作者：
Archin NM;Cheema M;Parker D;Wiegand A;Bosch RJ;Coffin JM;Eron J;Cohen M;Margolis DM
通讯作者：
Margolis DM
影响因子：
5.4
作者：
Hermankova, M;Siliciano, JD;Siliciano, RF
通讯作者：
Siliciano, RF
影响因子：
3.8
作者：
Sagot-Lerolle, Nathalie;Lamine, Aurelia;Lambotte, Olivier
通讯作者：
Lambotte, Olivier
影响因子：
1.5
作者：
Archin, Nancie M.;Espeseth, Amy;Margolis, David M.
通讯作者：
Margolis, David M.