Report from the 2012 International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies.

In June 2012, researchers and physicians from around the world gathered in Sitges, Spain, for the International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies. Below is a summary of the most clinically compelling presentations with respect to HIV medicine. (The entire abstract book is available in a supplement of Antiviral Therapy.) Resistance to Integrase Inhibitors: Raltegravir, Elvitegravir, and Dolutegravir Elvitegravir is an investigational integrase inhibitor currently being evaluated by the FDA, both individually and as part of the coformulated Quad pill. Previous studies identified six positions in integrase that are important for elvitegravir resistance, several of which are also important for raltegravir and, to a lesser extent, dolutegravir. In two separate industry-funded studies, Michael Abram, Kirsten White, and colleagues evaluated mutations that occurred at the time of elvitegravir failure [Abstracts 3 and 4]. They found extensive overlap in resistance patterns between elvitegavir and raltegravir, with considerable cross-resistance, even though the specific mutations commonly selected by each drug differed somewhat. For example, the Q148H mutation seems most important for raltegravir, but it was the Q148R mutation that gave the biggest effect for elvitegravir, followed by mutations at positions 92, 155, and 66. Furthermore, in a comparison of the Quad pill with Atripla (tenofovir/FTC/efavirenz), the researchers found that resistance to elvitegravir at the time of treatment failure was just as common as resistance to efavirenz. Although failure is uncommon with these regimens, resistance is likely to occur in about half of the failures. This is in stark contrast to boosted protease inhibitor–based regimens, where resistance is rarely seen at the time of failure. Not far behind elvitegravir in the pipeline is dolutegravir, which has broader activity than elvitegravir and is active against both elvitegravir- and raltegravir-resistant virus. In the industry-sponsored, single-arm VIKING-II study, patients with raltegravir-resistant virus …