The Holy Grail of the HIV community is a cure, while pharma persists in turning out new drugs—a critical need because with
lifelong multidrug treatment the standard of care, many people with HIV risk running out of options due to resistance, toxicity,
or price. The new class of integrase inhibitors is the main event on the calendar, as Gilead's elvitegravir and ViiV Healthcare's GSK 1349572 come online in 2013 and 2014, respectively. Along with Merck's first-in-class Isentress, these molecules, which thwart the
virus' effort to integrate its genome into the host cell's DNA, have the potential to disrupt the $10 billion market currently
in the hands of Gilead's megablockbuster fixed-dose combinations.
"Most of industry's focus right now is on second-generation integrase inhibitors," says McGill University's Matthias Gotte.
"It's the only new target that is panning out, and coming up with new and better versions of protease inhibitors and the other
classes is generally viewed as not cost-effective."
With no better efficacy than Isentress, and also sharing the same resistance profile, elvitegravir suffers from "too little,
too late" syndrome. But Gilead has shrewdly bundled it in a new adherence-friendly four-in-one pill dubbed the Quad, which, along with the biotech's upcoming Truvada/riplivirine fixed-dose duo, will establish the one-pill cocktail as the gold standard. By contrast, the integrase blocker in development
at ViiV, the GSK/Pfizer HIV joint venture, has gained "next big thing" status for its superior potency and unique resistance
pattern. ViiV is already behind schedule to meet its stated goal of one new drug a year, but its investment in HIV R&D has
the potential to revitalize this formerly on-a-mission field as it tests new non-nucleosides and new CCR5 inhibitors—classes
of dwindling interest to competitors.