New advance: Engineered immune cells seem to block HIV

Scientists claim they have safely introduced engineered immune cells in 12 people with HIV that have the ability to resist the virus.
Researchers are lauding it as a step toward paving the way to curing the disease. Typically, patients must stay on HIV treatments the rest of their lives.

"This reinforces our belief that modified T cells are the key that could eliminate the need for lifelong (antiretroviral drug therapy) and potentially lead to functionally curative approaches for HIV/AIDS," Dr. Carl H. June, Richard W. Vague Professor in immunotherapy in the department of pathology and laboratory medicine at Penn's Perelman School of Medicine in Philadelphia, said in a statement.
Researchers used so-called "zinc finger nuclease (ZFN) technology" -- what they referred to as "molecular scissors" -- to modify T cells in the immune system to mimic the CCR5-delta-32 mutation, a process called gene editing.
The CCR5-delta-32 mutation has been known to make people resistant to HIV, but is only found in about 1 percent of Caucasians. Timothy Ray Brown, known as the "Berlin Patient," had both HIV and leukemia, and was believed to be "cured" of AIDS after he had blood stem cells containing the rare mutation transplanted in 2007. He said in 2012 that he hadn't taken HIV medication since.
To create the mutation's effect, the researchers infused 10 billion SB-728-T cells into two groups of patients between May 2009 and July 2012. Between 11 and 28 percent of the T cells were modified with the ZFN technology. The gene editing limited the amount of CCR5 proteins that existed on the cells' surface. Without those proteins on the surface, HIV could not enter the T cells.

Within a week, all the patients saw a surge in their number of T cells due to the infusion. T cell numbers began to decline over the next few weeks, one of the hallmarks of HIV infection. Researchers observed that natural, unmodified levels of T cells declined, but the modified T cell numbers did not go down as much, suggesting they may have created HIV protection.
Six patients were taken off their antiretroviral drugs for up to 12 weeks starting four weeks after the infusions, while the other six stayed on the treatment.
The amount of HIV dropped in four of the patients who stopped treatment, one of whom had viral levels fall below the normal detection limits.That patient was later discovered to be a part-carrier of the CCR5 genetic mutation. The researchers said the subject could teach them more about the mutation in future studies.

The virus did return eventually in all the patients, but the researchers saw that the decline of the number of modified T cells was significantly less than the unmodified cells. The study's primary objective was to look at the infusions' safety.

CBS News medical correspondent Dr. Jon LaPook spoke with one of the 12 men in the program: Jay Johnson, 53, who has been living with HIV for more than two decades.

Three years later, the modified cells continue to circulate in Johnson's body and he continues to feel fine.

"It makes me very excited. Hopeful, and it makes me want to ... shout out to the world that there could be an end to this," said Johnson.

The new therapy approach may work where other recent attempts have failed. In July 2013, physicians at Brigham and Women's Hospital in Boston announced two HIV-positive men who had Hodgkin's lymphoma -- a type of blood cancer -- had no signs of the disease after receiving stem cell transplants. At the time of the announcement, each patient had been off medication for seven and 15 weeks. The stem cell donors in these two men's cases did not have the CCR5-delta32mutation.

In December, their doctors had announced the disease had come back in the Boston patients. The virus had lurked in disease reservoirs, which are areas of the body that store inactive HIV virus.
"The Boston cases show us that for the Berlin patient, it was not the chemotherapy or infusion of a donor's stem cells that staved off the HIV; it was the protection of the T cells by the lack of CCR5," Dr. Pablo Tebas, director of the AIDS Clinical Trials Unit at the Penn Center for AIDS research, said in a statement.
Since the Boston procedures couldn't completely eliminate the HIV reservoirs, the T cells were susceptible to infection once the HIV came back.
"The ZFN approach protects T cells from HIV and may be able to almost completely deplete the virus, as those cells are still functional," Tebas said.
The research was published online March 5 in the New England Journal of Medicine.
"The results from this small study are notable," wrote Dr. Mark Kay, a geneticist at Stanford, and Dr. Bruce Walker, an HIV researcher at the Raigon Institute in Boston, in an editorial published in the same journal issue.
They said the genome-editing technology might be used to treat other diseases than HIV, such as by fixing diseases caused by harmful genetic mutations.
"This proof-of- principle study is an important first step, not just in the treatment of those infected with HIV but also for genome editing in a broader sense," they added.

Source: http://www.cbsnews.com/news/gene-therapy-engineer-t-cells-block-hiv/ CBS Interactive Inc

By/Ryan Jaslow/CBS News/March 5, 2014

Doctors claim to have "functional cure" for HIV

CBS News/June 5, 2011, 8:15 PM
Thirty years ago from Sunday, the Centers for Disease Control issued the first report on the emerging AIDS epidemic. Now, after years of progress in holding back the disease, there is finally an apparent case of one successful cure.

CBS News correspondent Hank Plante, with San Francisco affiliate KCBS, reports that 45-year-old Timothy Ray Brown, now living in the Bay Area, tested positive for HIV back in 1995, but now has entered the scientific journals as the first man in world history to have his HIV completely eliminated from his body. It's what doctors call a "functional cure."

He was living in Berlin, Germany, in 2007, dealing with HIV and leukemia, when scientists there gave him a bone marrow, stem cell transplant that had astounding results.

"I quit taking my HIV medication on the day that I got the transplant and haven't had to take any since," Brown says, adding that his diseases are effectively gone.

In fact, his only medical problem these days is one involving his speech and motor skills because of neurological damage after the treatment, but that's getting better.
"The Berlin Patient," as Brown is known, received stem cells from a donor who was immune to HIV. In fact, about one percent of Caucasians are immune to HIV. Some say it goes back to the Great Plague; People who survived the plague developed an immunity, and that immunity was passed down to their heirs today.

Brown says being the first man to be cured of HIV makes him very, very happy.

Needless to say, Brown is now being monitored by doctors at San Francisco General Hospital and here at UCSF, where we sought out a medical opinion from one of the most respected AIDS researchers in the world, Dr. Jay Levy, who was one of the co-discoverers of the HIV virus.

"If you're able to take the white cells from someone and manipulate them so they're no longer infectable by HIV, and those white cells become the whole immune system of that individual, you've got essentially what we call a functional cure," Dr. Levy says.

We also sought out a medical opinion from Dr. Paul Volberding, another pioneering AIDS expert, who has studied the disease for all of its 30 years.

"One element of his treatment, and we don't know which, allowed apparently the virus to be purged from his body. So its going to be an interesting, I think, productive area to study," Dr. Volderding says. "He hasn't had any recurrence now for several years I think of the virus, and that hasn't happened before in our experience."

Timothy Brown's radical procedure may not be applicable to many other people with HIV, because of the difficulty in doing stem cell transplants, and finding the right donor. But this one case does open the door to the field of "cure research," which is now gaining more attention.

"I'm cured of HIV," Brown says. "I had HIV, but I don't anymore."
Those are words that so many in the scientific community are now cautiously clinging to.
. source: 2011 CBS Interactive Inc. http://www.cbsnews.com/news/doctors-claim-to-have-functional-cure-for-hiv/

Doctors say 'profound' new HIV treatment may prove the cure

Toxin Wipes Out Persistent HIV

An antibody-toxin combo kills residual HIV hiding out in the organs of mice.

Although anti-retroviral therapy is quite good at tamping down the viral load in the blood of people infected with HIV, the virus can still hang out in tissues. So researchers designed an antibody that seeks out a viral envelope protein expressed by infected cells and tacked on to this infection-homing device a toxin that destroys the cell. They tested the therapy on HIV-infected model mice and published their results in PLOS Pathogens this week (January 9). “Everywhere we look, the antibody is able to kill those infected cells,” University of North Carolina virologist J. Victor Garcia, a leader on the study, told the Los Angeles Times. In spleen, bone marrow, liver, lung, lymph nodes, and other areas, viral DNA dropped dramatically in mice administered the antibody-poison treatment, compared to animals given only conventional antiretroviral medications. “Our work provides evidence that HIV-infected cells can be tracked down and destroyed throughout the body,” Garcia said in a statement. John Frater, an HIV researcher from the University of Oxford, told The Conversation: “The conclusions at this stage are that in this mouse model, [antiretroviral therapy] can be potentially improved with the addition of an immunotoxin. How this translates to human treatment is not known. Also, whether this is a route for a cure strategy requires a number of other studies before any conclusions can be reached.”

Source: By Kerry Grens :- http://www.the-scientist.com/?articles.view/articleNo/38838/title/Toxin-Wipes-Out-Persistent-HIV/

Viral load tests ‘could transform HIV treatment failure’

The WHO has issued new HIV recommendations based on the latest research. Released yesterday (30 November), on the eve of World AIDS Day, the recommendations cover HIV treatment, prevention and infant feeding. The WHO now advocates starting antiretroviral therapy (ART) when the number of CD4 immune cells in a patient's blood — an indicator of immune system strength — falls to 350 cells per millilitre. In 2006, when the last set of recommendations was issued, the WHO advised starting ART at 200 CD4 cells per millilitre or lower, the point when patients start to exhibit disease symptoms. But research in the past three years has shown that early ART can reduce death rates. "We now have significant evidence and experience on when to start treatment, what drugs to use [in adults and adolescents] and what drugs to use for the prevention of mother–child transmission," Teguest Guerma, head of the WHO's HIV department, told SciDev.Net. "We have gathered a lot of evidence since 2006." Read more...

WHO updates HIV recommendations

The WHO has issued new HIV recommendations based on the latest research. Released yesterday (30 November), on the eve of World AIDS Day, the recommendations cover HIV treatment, prevention and infant feeding.
The WHO now advocates starting antiretroviral therapy (ART) when the number of CD4 immune cells in a patient's blood — an indicator of immune system strength — falls to 350 cells per millilitre.
In 2006, when the last set of recommendations was issued, the WHO advised starting ART at 200 CD4 cells per millilitre or lower, the point when patients start to exhibit disease symptoms. But research in the past three years has shown that early ART can reduce death rates.
"We now have significant evidence and experience on when to start treatment, what drugs to use [in adults and adolescents] and what drugs to use for the prevention of mother–child transmission," Teguest Guerma, head of the WHO's HIV department, told SciDev.Net. "We have gathered a lot of evidence since 2006." Read more

Building a Family Building a Bridge

A San Francisco couple adopts an Ethiopian orphan with help from Children’s Hospital’s International Adoption Clinic

The same week I had my uterine fibroids removed in a comfortable, modern Berkeley hospital, our future daughter, Asmina, was born in a small hut in southern Ethiopia. The next week I was home, with painkillers and my loving husband, Thierry, helping me recover. The week after Asmina’s birth, her birth father died, probably of AIDS,leaving his wife with their new baby and two other daughters, ages 3 and 5. Suspecting she also had AIDS, Asmina’s birth mother refrained from breast-feeding, hoping to reduce the chance the HIV virus would infect her baby.
One month after my surgery, I was hiking in the Rocky Mountains with my sister, while half a world away, Asmina’s birth mother had died. Sadly, no one in the village realized she had been so ill.
The three orphaned girls needed a caregiver, so somebody sent for their mother’s sister. It took her several days to walk to the children’s village. While the aunt could feed the older sisters injera bread, made from teff, the local grain, she could not feed injera to the baby.
A neighbor alerted a local social worker affiliated with Wide Horizons For Children, our adoption agency, telling her there was a baby next door who was not going to survive without help. The social worker and Asmina’s grandmother brought Asmina to an orphanage in Addis Ababa. When she arrived there, Asmina, 3 months old, weighed only a bit more than six and one half pounds.
But the nannies, nurses and director of the orphanage were wonderful,and soon Asmina was growing rapidly. She endured a couple of trips to the hospital for bouts of bronchitis and pneumonia, but our tough little cookie weathered those storms as well.
During all of this, we were unaware of Asmina’s existence and knew nothing of what she was going through. But three weeks after she arrived at the orphanage we got a phone call from our adoption agency: We had a daughter! We received a pixilated photo and some very scanty medical information.
We thought about adoption for years before actually taking our first steps to adopt. Both Thierry and I traveled widely while growing up, and our four parents were born in four different countries, on three different continents, so it felt natural to think about expanding our own family’s horizons with an international adoption.
At first we thought of making our family a mix of biological and adopted children. But when we started trying to have our own biological child, we ran into problems. After some difficult times, we decided not to go through the effort and uncertainty of a high-tech approach to dealing with infertility. Instead, we agreed to use our energies and money to bring into our lives a child who was already born and needed loving parents.
Once Asmina arrived at the orphanage, her blood was examined twice for hepatitis B,syphilis and HIV. All the tests came back negative. But we were perplexed by the HIV test results. The test methods used, ELISA (enzymelinked immunosorbent assay) and RST (rapid spot test), both measure the level of anti-HIV antibodies in the blood. Because it was believed Asmina’s mother had died of AIDS, we expected positive results from the antibody-based HIV tests; Asmina should at least have received maternal antibodies against HIV, even though she herself could be free of the virus. We had serious questions: could the clinical laboratory have made errors in its HIV analyses, and by extension, the others? Read more page 6-9....

Resource: children's hospital Oakland pg 6-9