Entry and Fusion Inhibitors: an Update

radication of hiv has not been possible with currently available reverse transcriptase inhibitors and protease inhibitors; and multiclass drug-resistant mutants of hiv—along with a multitude of disabling and sometimes life-threatening side effects—are a growing threat. Thus, there is a great need for compounds that target non-protease and reverse transcriptase elements of the hiv lifecycle. Not only might such novel therapies increase the potency of initial hiv treatment, but they may also provide hope for patients who have exhausted current treatment options. This article, based on prn lectures delivered by Drs. Joseph Eron and Christine Hogan in January 2002, reviews one of the most promising areas of hiv drug development: inhibitors of hiv fusion and entry. As reviewed by both investigators, two fusion inhibitors targeting hiv’s gp41 envelope protein (T-20 and T-1249) continue to advance through clinical trials and have both received fast-track designations by the U.S. Food and Drug Administration. As for other entry inhibitors targeting cellular proteins in the earlier stages of development (e.g., inhibitors of CD4, CCR5, and CXCR4), Drs. Eron and Hogan noted some of the advances and setbacks that have occurred over the past few years.