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Researchers See Signs of HIV Resistance in Gene Therapy


Overview

Originally Published: 03/06/2014

Post Date: 03/07/2014

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by Ron Winslow and Betsy McKay


Summary/Abstract

Development Called Promising Early Step in Hunt for Durable HIV Cure
he elusive quest for a cure for AIDS and the virus that causes it got a boost from two developments that amount to early but promising evidence that such a goal is achievable.

Content

Researchers at a conference in Boston said very early treatment in an infected baby may have sent the AIDS virus into remission, marking the second time than an infant born to an infected mother has possibly been cured by an aggressive regimen of drugs given shortly after birth.

That follows the report a year ago of a baby born in Mississippi who possibly had been cured by such treatment. That case was met with skepticism by some, but prompted doctors world-wide to try to figure out how to replicate it.

In the second development, researchers at the University of Pennsylvania said they successfully used a new gene-therapy technique on 12 patients in a strategy intended to make them resistant to HIV. The patients were all HIV-positive, and the effect of the treatment was transient, but the results showed that genetically modified cells persisted in the body and had other effects consistent with fending off a viral infection.

Various drugs are now available that can turn HIV infection into a chronic condition in which many patients can expect near-normal longevity.

But the drugs stop the virus from replicating—they don't eradicate it. Instead, the virus remains, hiding in so-called viral reservoirs in immune-system cells. If treatment is stopped, the infection almost always comes roaring back.

The new developments reflect fresh steps toward achieving a durable cure. It will take much more research to determine whether either strategy will help enable HIV-positive patients to stop taking antiretroviral drugs.

In the Penn study, published Wednesday in the New England Journal of Medicine, researchers used a technique called gene editing to block—or knock out—the effects of a gene called CCR5. HIV uses normal copies of the gene to gain entry to a patient's immune- system cells.

Previous research has shown that people who inherited a CCR5 mutation from both parents—a mutation that renders the gene inactive—don't become infected with HIV even after intense exposure to the virus. Less than 1% of people of European descent inherent both copies of the mutation; it isn't believed to affect people from other regions.

Excitement about CCR5 was heightened in late 2008 by the report of an apparent cure of an American AIDS patient named Tim Brown, known as the Berlin patient, after he received a bone marrow transplant for leukemia.

The bone marrow came from a donor with two copies of the CCR5 mutation and is viewed as the likely reason why Mr. Brown remains cured of HIV despite not having taken AIDS drugs since his transplant.

Expensive and risky, bone marrow transplants aren't a practical approach for a broad cure of the virus. But the Berlin patient's experience fueled interest in efforts such as those at Penn.

"The long-term goal is to replicate what happened to the Berlin patient," said Carl June, a Penn researcher and senior author of the study.

The 12 patients in the Penn study all were being treated with AIDS drugs. After the gene treatment, six went off therapy for as long as 12 weeks. In one case, evidence of HIV in the blood became undetectable. That patient turned out to have one copy of the CCR5 mutation, possibly explaining the response, said researchers, who noted that the trial was designed to test the technique's safety.

"It's an interesting scientific proof of concept," said Dan Barouch, professor of medicine at Harvard Medical School and researcher at Beth Israel Deaconess Medical Center in Boston who wasn't involved in the research. But, he added, "the clinical benefits to patients aren't yet clear."

The case of the second baby, who was born at a hospital in Long Beach, Calif., was reported Wednesday by Deborah Persaud, a professor of pediatrics and infectious disease at Johns Hopkins Children's Center in Baltimore.

She told the annual Conference on Retroviruses and Opportunistic Infections that the anonymous infant was put on antiretroviral drugs just four hours after birth. Six days later, levels of the virus had become nearly undetectable. Now 91/2 months old, the baby is essentially virus-free.

It would be impossible to say the child has been cured or even in remission because it remains on antiretroviral drugs, Dr. Persaud said.

Still, she said she was presenting the case to help clear skepticism that arose when the Mississippi case was presented last year, and that both are a "call to action" to develop a strategy for starting early treatment in infected infants. Dr. Persaud said she knows of five infants in Canada and two in South Africa who have been put on early treatment in addition to the two in the U.S.

A clinical trial is expected to begin in the next few months in which 54 infected babies will be put on AIDS drugs within 48 hours of birth.

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