California woman may be cured of HIV
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Sacramento resident Loreen Willenberg may be the first person to be cured of HIV without a bone marrow transplant, according to a recent medical journal report.
The new research suggests that Willenberg's virus and that of some five-dozen other people with long-term untreated HIV is so remotely hidden away in their genome that it cannot be used to produce new virus. Researchers were unable to find any intact virus in more than a billion of her cells.
"I believe Loreen might indeed meet anyone's definition of a cure," Dr. Steven Deeks of UCSF, one of the co-authors of the Nature article, told the Bay Area Reporter. "Despite heroic efforts, we just could not find any virus that is able to replicate. Her immune system seems completely normal. Even her HIV antibody levels are low, which is unprecedented in an untreated person."
Willenberg, who was diagnosed in 1992, is well known among advocates as a so-called elite controller, a small subset of people with HIV who are naturally able control the virus without antiretroviral treatment. They are thought to make up less than half a percent of all HIV-positive people.
The only two people widely considered to have been cured of HIV — Palm Springs resident Timothy Ray Brown and a London man, Adam Castillejo — received bone marrow transplants from a donor with a rare genetic mutation that makes cells resistant to HIV entry. But this procedure is far too dangerous for people who do not need it to treat advanced cancer.
A team led by Dr. Xu Yu of the Ragon Institute of Massachusetts General Hospital, the Massachusetts Institute of Technology, and Harvard analyzed integrated HIV in millions of cells from 64 elite controllers and 41 typical HIV-positive people on antiretroviral treatment recruited at Mass General and Zuckerberg San Francisco General Hospital.
Using next-generation gene sequencing, the researchers analyzed where the participants' HIV blueprints are located their chromosomes. They found that the virus in elite controllers is locked up at remote sites in the genome, far from elements that are needed for viral replication.
In Willenberg's case, after analyzing more than 1.5 billion of her peripheral blood immune cells, the researchers could not find any intact HIV capable of producing new virus.
It is unclear why this "block and lock" phenomenon happens only in a small proportion of HIV-positive people. It's possible that the virus ends up being hidden away by chance, but the researchers think it's more likely that the HIV sequestered in these remote sites is evolutionarily selected as the immune system eliminates more accessible virus.
The San Francisco patient
Yu first presented the research at last summer's International AIDS Society Conference on HIV Science in Mexico City, where Willenberg was referred to as the "San Francisco Patient" because she participated in research in the city. Last October, she went public with her status in a news report excerpted in the B.A.R.
"I can only hope and pray that with continued dedication we can figure out how I have dumped the virus into the DNA junkyard," she told advocates on a web forum soon thereafter. "Maybe they can reverse engineer it and figure out what's flipped on in me that's flipped off in others."
The question now is whether it might be possible to develop treatments that could help the millions of people with normally progressing HIV to become elite controllers like Willenberg.
"The key question is how did her immune system achieve this remarkable state," said Deeks. "We do not know. We need to find more people who are exceptional controllers like Loreen and get to work on figuring out the mechanism."
Willenberg, who founded the Zephyr LTNP Foundation as a support network for HIV controllers and long-term non-progressors, is willing to do her part, having participated in more than a dozen studies over the years.
"No one is more amazed than I am that my immune system is one of the most efficient known to science," she told advocates. "I will continue to volunteer as long as they need me. Hopefully, if there's one of me, there are others, and I'll do what I can to help find them."
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