《HIV对CCR5抑制剂的反应：强化而非转换》

• 来源专题：艾滋病防治
• 编译者： 李越
• 发布时间：2005-04-16
• 原文来源：http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122263

Treatment of HIV infection has been revolutionized by the development of potent inhibitors of critical viral enzymes, particularly the HIV-1 reverse transcriptase and protease (1). Appropriate combinations of such drugs (referred to as highly active antiretroviral therapy or HAART) markedly suppress viral replication in most treated persons, leading to significant restoration of immune system function. In the developed world, HAART is responsible for dramatic reductions in HIV-associated morbidity and mortality. However, the quest for improved therapies continues, because of problems that seriously limit the current HAART regimens, including toxic side effects, viral persistence, difficulties in adhering to treatment, high cost, and the emergence of drug-resistant escape variants. The resistance problem is particularly challenging because of the extraordinarily high HIV-1 mutation rate, and the ability of viral variants harboring resistance mutations in both reverse transcriptase and protease to continue replicating in vivo. The viral mutability provides a rationale for developing anti-HIV drugs that target components of the host cell machinery essential for viral replication, because such molecules would not mutate in the face of drug pressure. The cellular receptors involved in HIV-1 entry are receiving special attention, with numerous candidate inhibitors at various stages of clinical development . However, HIV-1 finds ways to escape such inhibitors. In a recent issue of PNAS, Trkola et al. analyze the mechanism by which HIV-1 escapes in vitro from a low molecular weight inhibitor targeted against the CCR5 coreceptor. The findings raise important questions not only about the clinical applications of this novel class of anti-HIV agents, but also about coreceptor usage in HIV-1 disease.