UCSF researchers recently gave an overview of their latest work launching a new Institute for HIV Cure Research, funded by a $20 million grant from amfAR, the Foundation for AIDS Research. Cure studies will also be a key theme of the Conference on Retroviruses and Opportunistic Infections and accompanying Community Cure Research Workshop coming up in February.
"We recognize that realistically we're not talking about delivering a cure to everyone who needs it by 2020," amfAR CEO Kevin Frost said at the HIV Cure Summit last month on World AIDS Day. "We believe a cure is evolutionary �" we want to build the foundations and understand the science of what it takes."
UCSF was chosen to host the new institute, which will be headquartered at the Mission Bay medical campus, in a national competition. Frost stressed that the $20 million allocated for the first five years is "a floor, not a ceiling."
"The San Francisco area has a higher concentration of scientific thought leaders in HIV than anywhere else in the world," said Rowena Johnston, amfAR vice president and director of research. "The Bay Area has consistently led the way in developing and implementing scientific advances in HIV prevention and treatment, and the potential for this team of researchers to develop a cure is unparalleled."
"San Francisco has a long and storied history of response to the HIV epidemic," added UCSF Center for AIDS Research director Dr. Paul Volberding, who will also head the new institute. "This will bring together a broad team of leading scientists who believe a cure is possible, and that it will happen here. We're ready to end this epidemic."
Scientific foundations
Effective combination antiretroviral therapy, which debuted in the mid-1990s, has made HIV a chronic manageable disease for most people with access to treatment �" in many cases using once-daily single-tablet regimens. But the drugs are not a cure, and if they are stopped the virus soon comes back. Even during treatment inactive HIV genetic material remains hidden in the body, and this low-level virus can cause inflammation that contributes to conditions such as cardiovascular disease and cancer.
"I don't talk to any patient who wouldn't rather be cured than take one pill once a day," Volberding said at the summit.
The past couple of years have seen some setbacks in the cure field, including the return of HIV in the "Mississippi baby," a child infected before birth who started antiretrovirals very early and was thought by many to be cured.
This leaves only one person �" former San Francisco resident Timothy Brown, known as the Berlin Patient �" who appears to have been truly cured of HIV. Brown has no detectable HIV in his blood or tissues more than eight years after receiving bone marrow transplants from a donor with a natural mutation that makes T-cells resistant to infection.
Researchers have tried various approaches to curing HIV, including very early antiretroviral treatment, mimicking Brown's cure by protecting cells from infection, flushing the virus out of hiding and destroying it �" a strategy known as "shock and kill" �" and strengthening the natural immune response against the virus.
Many researchers now speak of a "functional cure" or remission, rather than completely eliminating HIV from the body, and most experts think a combination of approaches will be necessary.
"Let's get to a place where we don't have to take medications every day, where we don't have to experience the side effects of the medications, and where we can get our immune systems to a state where we're not at a risk of early aging," said longtime AIDS survivor and advocate Matt Sharp, speaking on a KQED program announcing the new institute. "But overall, of course, I'd like to see HIV completely eradicated from my body."
The HIV Cure Summit featured an overview by Johnston, followed by the researchers who will lead the four teams comprising the new institute.
"HIV is like a lawn," Johnston explained. "You can mow it and keep it under control, but that doesn't get at the roots."
Warner Greene, Ph.D., director of UCSF's Gladstone Institute of Virology and Immunology, will head an effort to study how so-called reservoirs of hidden HIV are established and persist in the body.
"Our strategy will be to exploit the innate immune system to help flush the virus out of hiding and ultimately to eliminate its ability to bounce back when drug treatment ends," said Greene, who is investigating how molecules known as TLR agonists set off immune activation, including activation of the T-cells that harbor latent HIV. "We may not be able to get every last virus, but maybe we can get to a low enough level that the immune system can control it."
Dr. Mike McCune and his team aim to figure out precisely where HIV hides within specific tissues in the body �" including how viral reservoirs differ between men and women �" while a group overseen by Satish Pillai, Ph.D., will work on better ways to measure hidden virus that is capable of replicating.
Finally, UCSF Professor Dr. Steven Deeks and his team will study how TLR agonists affect HIV reservoirs in the tissues of patients on antiretroviral treatment.
"With the support of the community in San Francisco, I think we have a responsibility to take these [ideas] quickly into the clinic, to quickly identify approaches that we can safely bring into human trials," Deeks said. "We're doing this differently than the traditional academic approach. We want to make an impact, so we're using a bit of an industry approach to move things into the clinic within the next four or five years."
Deeks predicted that the "next big game changer" will be long-acting injectable antiretrovirals that last one or two months. "This will have a huge impact on people who cannot take pills on a daily basis," he said, "but it will not be a substitute for a cure."
More cure research at CROI
This year's CROI meeting will take place February 22-25 in Boston. The Community Cure Research Workshop on February 21, co-sponsored by the AIDS Treatment Activists Coalition; European AIDS Treatment Group; AVAC, a global HIV prevention advocacy group; Treatment Action Group; and Project Inform, will feature an overview for advocates of recent advances in the field and community strategy sessions to discuss how to promote cure research.