Cutaneous toxicities of antiretroviral therapy for HIV Part I. Lipodystrophy syndrome, nucleoside reverse transcriptase inhibitors, and protease inhibitors
Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. Journal of the American Academy of Dermatology
(Impact Factor: 4.45).
10/2010; 63(4):549-61; quiz 561-2. DOI: 10.1016/j.jaad.2010.01.061
Antiretroviral medications for the treatment of HIV are common drugs with diverse and frequent skin manifestations. Multiple new cutaneous effects have been recognized in the past decade. Dermatologists play an important role in accurately diagnosing and managing the cutaneous toxicities of these medications, thereby ensuring that a patient has as many therapeutic options as possible for life-long viral suppression. Part I of this two-part series on the cutaneous adverse effects of antiretroviral medications will discuss HIV-associated lipodystrophy syndrome, which can be seen as a result of many antiretroviral medications for HIV, and the specific cutaneous effects of the nucleoside reverse transcriptase inhibitors and protease inhibitors.
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ABSTRACT: Currently the long-term usage of traditional anti-HIV drugs, such as nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), eventually leads to the emergence of drug resistance and severe side effects. Thus it is imperative to design and develop more promising HIV-1 inhibitors to overcome these drawbacks. Fortunately, with the identification of some fascinating targets in the entry process of viral life cycle, HIV-1 entry inhibitors (EIs) with low cytotoxicity and mild side effects turned out as novel and effective anti-HIV agents. Especially, of these potent EIs, small molecule CCR5 antagonist maraviroc was approved by US FDA in 2007, which significantly increased the therapeutic options for the clinical treatment of HIV-infected patients. Subsequently, as promising anti-HIV drug candidates, kinds of small molecule CCR5 antagonists have been synthesized and evaluated in clinical trials. In this article, current progress in the development of novel small molecule CCR5 antagonists will be reviewed on the basis of their chemical structures with a special attention to their discovery stories. Simultaneously, binding mode analysis based on molecular modeling studies will also be introduced.
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