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EPIDEMICS
Taking 'scissors' to immune cells shows HIV promise
by Staff Writers
Washington (AFP) March 05, 2014


Second US baby is HIV-free after early treatment
Washington (AFP) March 05, 2014 - A baby treated for HIV within hours of birth is free of the virus nearly a year later, in the second case that has raised hopes about early treatment, doctors said Wednesday.

The approach mirrored that taken for a Mississippi baby, who has been off treatment for 21 months and still has no detectable virus in her system.

The latest research on the two young girls was presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

The newest case involves a Los Angeles baby was born to a mother infected with HIV and who had not been taking her medications, making her at high risk for transmission, said Yvonne Bryson, chief of pediatric infectious diseases at the David Geffen School of Medicine at the University of California, Los Angeles.

Audra Deveikis, a pediatric infectious disease specialist at Miller Children's Hospital Long Beach, where the baby was born, tested the infant and gave her high, treatment-level doses of antiretroviral drugs before even knowing if she was HIV-positive, Bryson told AFP by phone from the conference.

"The way it works is you test and you treat before you know the results because it takes several days to get the results," explained Bryson, a consultant on the case.

Treatment started at four hours of age, even earlier than the Mississippi child.

Eventually, the tests came back positive for HIV.

But by six days of age, the virus was undetectable.

"The remarkable thing about this particular baby is that the virus disappeared so quickly," said Bryson.

- Not a 'cure' yet -

The baby is still being treated with antiretroviral drugs, and researchers are cautious not to utter the world "cure" or even "remission" just yet.

Now aged 11 months, the child is doing well and continues to see doctors while under the care of a foster family.

She has "no detectable viral load, nothing since six days of age. That is the earliest ever," said Bryson.

Once she turns two, doctors may decide to stop suppressive therapy to see if she is in remission, or if the virus would rebound.

"The only way we would know if the baby is in remission is to stop therapy," explained Bryson.

Also at the conference, Deborah Persaud of Johns Hopkins University presented the latest on the Mississippi baby, who was given ART at 31 hours of age.

Now, the three-year-old is considered in remission from HIV, after drug treatment was stopped 21 months ago and no viral rebound has been observed.

Bryson said the Los Angeles team is optimistic that their baby will do just as well.

"The fact that it was a very fast reduction in the virus to undetectable levels makes us very hopeful that this baby might follow in the footsteps of the Mississippi which is still being followed," said Bryson.

"We are learning a lot now and it is exciting for the future."

There is no known cure for AIDS, which has infected some 70 million people around the world and killed 35 million, according to the World Health Organization.

A new gene therapy approach that engineers a person's T cells so that they become resistant to the human immunodeficiency virus has shown early signs of success, researchers said Wednesday.

Also called gene editing, the process acts like molecular scissors to snip off an entry portal for HIV so the virus cannot enter these key immune cells.

Once the cells lack the CCR5 protein, the immune system behaves much the way it does in a rare set of people -- about one percent of the population -- who are born with a genetic mutation that prevents them from getting HIV.

Experts say the development puts researchers a step closer on the path toward curing AIDS, which has infected nearly 70 million people and killed some 35 million worldwide.

"This study shows that we can safely and effectively engineer an HIV patient's own T cells to mimic a naturally occurring resistance to the virus," said senior author Carl June of the University of Pennsylvania.

- Repopulating the immune system -

Researchers re-infused 12 patients with their own modified cells and saw them persist in the body, essentially repopulating their immune systems.

Based on the phase I trial results reported in the New England Journal of Medicine, the technique was described as "generally safe."

One serious adverse event was reported in a patient who was rushed to the emergency room with fever, chills, joint pain and back pain within 24 hours of infusion.

Researchers said the problem was likely a reaction to the study drug. All patients completed the 36-week study and are being monitored for the next 10 years.

The treatment also decreased, at least temporarily, the viral loads of some patients taken off antiretroviral drug therapy, or ART.

The patients were each given a single infusion of about 10 billion cells between May 2009 and July 2012.

A dramatic spike in modified T cells was seen in the patients' bodies a week after the infusion.

Six people were taken off ART for up to 12 weeks, beginning four weeks after infusion, and the other six patients remained on treatment.

Four of the patients who stopped ART saw their viral loads drop.

One patient's viral load dropped so low that it became undetectable. Researchers later discovered the person had inherited the CCR5 delta-32 gene mutation from one parent, essentially giving the patient a head start on the treatment.

- A step toward a cure? -

Co-authors on the study came from the Albert Einstein College of Medicine and Sangamo BioSciences, which developed approach for editing the cells, known as zinc finger nuclease (ZFN) technology.

June said he hopes that modified T cells, an experimental approach that has also shown promise against some forms of leukemia, could one day lead to a functional cure for HIV/AIDS and eliminate the need for daily antiretroviral therapy.

So far, only one man -- American Timothy Brown, often called the Berlin patient -- has been cautiously considered cured of HIV after undergoing a bone marrow transplant from a donor with a natural genetic mutation against HIV. He has been off ART since 2008.

Researchers have been trying for years to find a way to replicate those results for the wider population, in a way that might be safer than a risky bone marrow transplant, which carries a 30 percent risk of death.

While the road to a cure is still long, experts praised the research for making significant advances.

"If gene therapy were found to be a way to cure HIV, I really do believe that somebody is going to come up with a way that it could be delivered," Rowena Johnston, vice president and director of research at The Foundation for AIDS Research, or amfAR, told AFP.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which contributed funding to the research, described it as "clearly promising."

"But you have got to be careful that you don't at this point declare any victory because we are still far from any widespread applicability," Fauci said.

Tests to start on ring to prevent pregnancy and HIV
Chicago (AFP) March 05, 2014 - Clinical trials are to begin soon on a new vaginal ring that promises to provide months of protection against pregnancy, HIV and herpes, US researchers said Wednesday.

The device, which is similar to birth control rings already on the market, delivers both an antiretroviral drug and a contraceptive which are slowly released over 90 days.

A report on the ring and how it was developed by scientists at Northwestern University is published in the peer-reviewed journal PLOS ONE.

The ring could offer women an alternative that eliminates the anxiety of missed pills and requires a lower dose of an antiretroviral drug aimed at preventing HIV since it is delivered at the point of transmission.

Scientists and AIDS prevention advocates have been trying to develop a ring like this for a long time, said Rowena Johnston, vice president and director of research at amfAR, the Foundation for AIDS Research.

"If you have something that is long acting that people don't have to think about every time they have sex but something that is in place, that is thought to be a boon," she told AFP.

While the ring is only designed to protect against transmission during vaginal sex, it could be a valuable tool for some women, she said.

"And it is probably not easily detected by the male partner, if that is important to you," Johnston added.

Both drugs released by the ring -- levonorgestrel and tenofovir -- are already used to prevent pregnancy and the spread of HIV.

Tenofovir -- which inhibits HIV and herpes replication in susceptible cells -- is taken orally by 3.5 million HIV-infected people worldwide.

It has been found to help prevent HIV infection as well, but so far only with pills that must be taken daily.

A gel which delivers tenofovir has been found to be somewhat effective in clinical trials but the gel needs to be inserted into the vagina before and after sex.

Many of the women in the clinical trials did not use the gel every time they had sex.

"Products only work when they are used," said study co-author David Friend, product development director at CONRAD, which develops reproductive health technologies for low-income countries and is affiliated with Eastern Virginia Medical School.

"By having a ring that can remain in the body for up to 90 days, our hope is that this ring will offer a solution to increase adherence, and therefore provide greater protection against HIV while also preventing pregnancy," Friend said.

The differences between the two drugs presented a "huge" design challenge, said Northwestern University biomedical engineer Patrick Kiser, who holds the ring's patent.

Tenofovir dissolves easily whereas the contraceptive drug levonorgestrel is highly insoluble. The drugs also had to be delivered in drastically different -- but consistent -- doses.

"A lot of engineering has gone into developing the ring," Kiser said.

The ring uses a new kind of polymer -- or chain of molecules -- that swells in the presence of bodily fluids and is capable of delivering up to 100 times more tenofovir than current intravaginal rings.

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