期刊
EXPERT OPINION ON DRUG DISCOVERY
卷 3, 期 11, 页码 1345-1361出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/17460441.3.11.1345
关键词
antiretroviral; aplaviroc; ART; CCR5; HAART; HIV-1; INCB9471; maraviroc; PF-232798; resistance; SCH-532706; TAK-220; TAK-652; TAK-779; Trofile (TM); tropism; vicriviroc
Background: The human immunodeficiency virus 1 (HIV-1) is the causative pathogen of AIDS, the world's biggest infectious disease killer. About 33 million people are infected worldwide, with 2.1 million deaths a year as a direct consequence. The devastating nature of AIDS has prompted widespread research, which has led to an extensive array of therapies to suppress viral replication and enable recovery of the immune system to prolong and improve patient life substantially. However, the genetic plasticity and replication rate of HIV-1 are considerable, which has lead to rapid drug resistance. This, together with the need for reducing drug side effects and increasing regimen compliance, has led researchers to identify antiretroviral drugs with new modes of action. Objective: This review describes the discovery and clinical development of CCR5 antagonists and the recent approval of maraviroc as a breakthrough in anti-HIV-1 therapy. Conclusion: CCR5 inhibitors target a human cofactor to disable HIV-1 entry into the cells, and thereby provide a new hurdle for the virus to overcome. The status and expert opinion of CCR5 antagonists for the treatment of HIV-1 infection are detailed.
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