Three years ago, Warner Greene was among a number of HIV experts meeting at George Washington University to discuss the problem of HIV “latency”—the tendency of the virus that causes AIDS to hide in cells and then rage up when drug therapy is halted. “I made a plea,” recalls Greene, head of virology and immunology research at the Gladstone Institutes, a biomedical research institution affiliated with the University of California at San Francisco. Rather than maintaining separate and often competitive research efforts, he said, universities should join with government research agencies and drug companies to try to solve the problem together. “The world ‘collaboratory’ came out of nowhere,” Greene says.
From that discussion emerged the Martin Delaney Collaboratory—a consortium that includes academic researchers from several universities, as well as Merck, the Whitehouse Station, NJ-based drug giant that has made HIV research a priority. The National Institutes of Health (NIH) is funding the effort. On July 11, Merck announced that it would participate in a five-year effort with UCSF to solve the problem of HIV latency, funded by $5.6 million from the Collaboratory, which was named in honor of HIV activist Martin Delaney, who died in 2009. Separately, Merck said, it will participate in another multi-institutional research project led by the University of North Carolina and funded by the Collaboratory.
Merck won’t receive any money for participating, though it will share intellectual property rights with members of the consortia on any discoveries that come out of the effort, says Daria Hazuda, vice president of Merck Research Laboratories. More importantly, she says, Merck will have access to an HIV brain trust that could unlock a mystery that has confounded the field for years. “If we want to cure HIV, we have to define the problem of latency,” she says. “We need to understand where the virus is hiding and how it sleeps in cells.”
The outlook for HIV patients has greatly improved thanks to the two dozen or so anti-viral treatments on the market, which include Merck’s own raltegravir (Isentress) and indinavir (Crixivan). Problem is, says Hazuda, “They suppress the virus, but they don’t cure the infection.” That’s because the virus hides in reservoirs—specific cells that harbor HIV.
The various members of the Collaboratory are focusing on different aspects of combating HIV latency. UCSF’s Gladstone is zeroing in on understanding the molecular basis of HIV latency. Greene says two types of cells that the virus hides in have already been identified: transitional memory T cells and central memory CD4 T cells. With the new funding and Merck’s participation, he says, “We’re going to look very hard to see if the virus is lying low in other cells we don’t know about.”
Galdstone will also work closely with Merck to try to discover small-molecule drugs that can wake up the sleeping virus and ultimately eradicate it. Greene imagines a drug cocktail will be necessary, which is why the involvement of a pharmaceutical company is so vital, he says. “Merck brings so much drug-development experience,” Greene says. “Their library of molecules, their instruments, their ability to do pharmacological research—that will all be key.”
Although such a cocktail might not cure HIV, Greene says, “Maybe we can reset the immune system so patients can control the disease when they come off the drugs.” That’s especially important in the developing world, he adds, where cost constraints make it difficult to keep patients on drug cocktails for years on end.
When asked whether drugs will be able to eradicate HIV reservoirs, Hazuda responds with cautious optimism. “It does look like there are multiple avenues by which the virus remains hidden. So multiple approaches in parallel will be needed,” she says. “Can it be solved with drugs? I’m always an optimist. But I don’t think there will be one magic bullet.”
All told, the Delaney Collaboratory is providing $14 million a year for up to five years to three research consortia that are all working on the problem of HIV latency. Merck is among a handful of drug companies participating in the effort. “Even in the early days, we worked closely with academia to understand the basic biology and biochemistry of HIV,” Hazuda says. “We need to expand those relationships and be very highly collaborative, so we can assess how effective the interventions we’re thinking about really are.”