News (Updated June 20, 2010)

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New Gene Therapy Hope for HIV

June 18, 2010

Researchers Say Engineered Stem Cells Could Offer One Shot Replacing Multiple Daily Medications

(Discover)  When it comes to research on HIV and AIDS treatments, it can be hard to know when to celebrate a small advance-everyone wants to see progress, but so many experimental avenues that seemed promising have turned out to be dead ends. Still, a new study that tried a sophisticated form of gene therapy as an HIV treatment seems cause for cautious optimism. If it bears out under further testing, the technique could lead to a one-shot, long-lasting treatment that could replace the punishing regimen of daily medications.

Treating HIV currently comes down to controlling the viral load with a mixture antiretroviral drugs, but over time, this drug cocktail becomes less effective. Researcher John Rossi and his colleagues tried to craft a more permanent treatment by genetically modifying the HIV-infected patients’ own blood stem cells and increasing the cells’ ability to fight off the virus. The researchers weren’t able to truly combat the virus in this experiment-the patients’ viral loads remained the same-but their work moved beyond previous attempts in two ways: They successfully modified blood stem cells by giving them anti-HIV genes, and those cells survived for two years in patients.

According to ScienceNow: Earlier clinical studies the group conducted with the same strategy made little headway, but now the researchers have overcome two key obstacles, says Rossi, a molecular geneticist. One is that they managed to stitch the anti-HIV genes into a high percentage of the appropriate stem cells. The other is that the cells lived for a long time. “If we could increase the number of modified cells by 10- or 100-fold, we might be able to stop the virus itself,” says Rossi.

The small study published in Science Translational Medicine tested the safety of the technique for HIV-infected patients, and served as a proof of concept. The four patients in this study were undergoing therapy for AIDS-related lymphoma at City of Hope cancer center in California . Part of the usual treatment for this condition is to remove blood stem cells (found in bone marrow) before cell-damaging chemotherapy, and to then return them after treatment. Researchers wanted to test their virus-fighting cells’ survival skills, so with each patient’s normal blood stem cells, the researchers also reintroduced a small number of modified cells.

"They modified the cells in three ways: They boarded up the cells’ doors to keep the HIV virus out, and made two genetic changes to the cells’ internal defenses so that the virus would have a harder time copying itself if it made it through," according to ScienceNow.

As a safety precaution, the researchers didn’t implant enough of these novel cells to test how well they might fight the virus, but they did get a glimpse of how long the modified cells could stay in a person’s system. Up to two years after the treatment, patients still had low levels of these special cells.

“That’s a major finding,” Rossi added. While the number of cells expressing those genes was too low to provide any therapeutic benefit, it’s “proof of principle” that gene therapy may provide long-term HIV treatment, he said.

As a next step, researchers hope to implant a greater number of modified cells in patients, to see how well they can fight and how long their defenses hold.

 

Nurse-Based Care Comparable to Physician-Based Care in HIV Treatment

Emma Hitt, PhD

June 17, 2010 — Nurse-managed care of patients receiving antiretroviral therapy (ART) for HIV may result in comparable outcomes to physician-managed care and enable expanded access to care in resource-poor settings.

Ian Sanne, MD, from the University of the Witwatersrand, in Johannesburg , South Africa , and colleagues with the Comprehensive International Program for Research in AIDS in South Africa conducted a randomized noninferiority trial at 2 South African primary-care clinics. They published their findings online June 16 in The Lancet.

According to Dr. Sanne and colleagues, a shortage of 4.3 million health workers (ie, physicians, midwives, nurses, and support workers) exists worldwide, and only 17.4 medical practitioners, most located in urban areas, are available to treat 100,000 people in South Africa .

To compare outcomes of nurse vs physician management of physician-initiated ART care for HIV-infected patients, researchers randomly assigned HIV-positive individuals with a CD4 cell count of fewer than 350 cells per microliter or World Health Organization (WHO) stage 3 or 4 disease to ART care monitored by either nurses (n = 404) or physicians (n = 408).

Treatment failure was defined as a composite of the following endpoints: traditional virological failure, occurrence of dose-limiting toxic effects, death, and all clinic losses that translated to failure of the treatment strategy to maintain patients on ART.

Of the patients, 46% demonstrated treatment failure — 48% in the nurse group and 44% in the physician group (hazard ratio, 1.09; 95% confidence interval, 0.89 - 1.33), which was within the limits for noninferiority.

Other outcomes at a median follow-up of 120 weeks were also comparable between the nurse- and physician-monitored patients, including deaths (10 vs 11), virological failures (44 vs 39), toxicity failures (68 vs 66), and program losses (70 vs 63).

According to the researchers, approximately 16% to 17% of patients were considered treatment failures because of the dose-limiting toxic effects of stavudine, which included a high frequency of lipomorphological changes and lactate increases.

"WHO and South African guidelines have moved away from reliance on stavudine; however, this drug remains widely used in resource-poor HIV therapy programmes," they write. "The dose reduction of stavudine to 30 mg after the first year of the study, which was in line with WHO recommendations, might have reduced drug-limiting toxic effects," they add.

“The results of this study lend support to the expanded access to treatment with use of models of task shifting in primary health care," the authors conclude.

Independent commentators Mark Boyd, MD, from National Centre in HIV Epidemiology and Clinical Research and St Vincent’s Hospital, , Sydney, Australia, and Chidi Nwizu, MBBS, from the University of Maryland School of Medicine, in Baltimore, point out that "it is marvellous to see the results of a practical and innovative study which helps propel the field forward and improves our collective confidence that despite all the obstacles we can succeed."

However, they add that many HIV-infected patients reside and access care in rural areas. "The study sites in [the Comprehensive International Program for Research in AIDS in South Africa ] were not rural and had reasonable access to laboratories and ancillary services," they write. "These are potential challenges in decentralisation models that include task-shifting."

The study was supported by the National Institutes of Health, the US Agency for International Development, and the National Institute of Allergy and Infectious Diseases. The authors and Dr. Nwizu have disclosed no relevant financial relationships. Dr. Boyd serves on an HIV advisory board for MSD Australia and for Bristol-Myers Squibb Australia; has received funding and/or has partnered with Merck, Abbott, and the American Foundation for AIDS Research; and has spoken at events for Abbott and Merck, received honoraria from MSD Australia and Janssen-Cilaq Australia, and serves as vice president of the Australasian Society for HIV Medicine.

Lancet. Published online June 16, 2010.

 

Study reveals promise for HIV test

Early detection hope of S.D. researchers

By Keith Darcé, UNION-TRIBUNE STAFF WRITER

Tuesday, June 15, 2010

Dr. Sheldon Morris of UCSD’s Antiviral Research Center helped 
develop a new test for HIV that identifies the virus much earlier than 
previous tests.

Earnie Grafton / UNION-TRIBUNE

Dr. Sheldon Morris of UCSD’s Antiviral Research Center helped develop a new test for HIV that identifies the virus much earlier than previous tests.

BY THE NUMBERS

1.1 million: People living with HIV in the United States .

232,344: Estimated number of Americans infected with HIV who don’t know it.

3,847: People in San Diego County infected with HIV between April 2006 and December 2008.

56,300: Americans who become infected with HIV each year.

14,000: Americans who die of AIDS each year.

46 percent: Portion of people with HIV who are black.

18 percent: Portion of people with HIV who are Latino.

Sources: Centers for Disease Control and Prevention; San Diego County Health and Human Services Agency

The evolution of AIDS from a deadly disease shrouded in fear to a largely manageable condition took another step forward Monday, when San Diego researchers unveiled results of a study looking at an early-detection method for the virus that causes the illness.

The report’s authors said a rarely used blood test can spot HIV weeks before the body recognizes the infection. They recommended that it be offered along with the more common screening method to people at high risk of contracting the virus, including gay men, intravenous drug users and people with multiple sex partners.

Among the 3,151 participants in a two-year study, the blood test identified HIV in 15 individuals who had falsely tested negative with the traditional saliva swab procedure.

False negative results occur in as much as 1 percent of those who take the swab test, which pinpoints antibodies produced by the immune system in response to infection. It can take as long as three months for the body to begin producing enough antibodies to trigger a positive reading.

During that lag time, people can unknowingly spread HIV through unsafe sex and miss early treatments that could improve their health in the long run, said Dr. Sheldon Morris, an AIDS researcher at the University of California San Diego ’s Antiviral Research Center in Hillcrest.

Morris was lead author of the HIV-testing report, which appeared Monday in the journal Annals of Internal Medicine. His colleagues included other researchers from UCSD and San Diego County ’s HIV, STD and Hepatitis Branch.

“If people got an antibody test alone and were told they weren’t infected when they were, they could be a strong infection risk until they get tested again, which according to guidelines could be six to 12 months later,” Morris said.

The latest findings reinforce similar conclusions from a 2005 study led by scientists at the University of North Carolina . Those researchers administered the early-detection blood test to a much larger sampling of people.

Participants in the San Diego study whose blood tested negative could get their results in person, through an automated telephone system or by logging on to a secured website. About 65 percent of those who sought their results used the automated options.

Morris said the pattern demonstrates a shift in attitudes about AIDS. The illness once was viewed as a death sentence that needed in-person counseling to deal with issues such as shame and secrecy. But advances in detection and treatment have turned it into a chronic, controllable condition for most patients — not unlike diabetes.

“HIV is not as mysterious as it once was,” Morris said.

The early-detection blood test, which homes in on nucleic acid RNA molecules produced by the virus, has been used to screen most of the nation’s blood donation supply since 2002, according to its maker, Gen-Probe of San Diego .

The FDA approved the test for use as an HIV diagnostic tool in late 2006, but its cost — as high as $100 — and more complicated administration have helped discourage widespread use, said Rowena Johnston, vice president and research director of the New York-based international HIV/AIDS research foundation known as AMFAR.

Samples for the blood test are obtained through finger pricks and must be sent to a laboratory, which can take up to two weeks to return results.

“The reason the antibody test is (widely) used is because of low cost and convenience,” Johnston said. The saliva swab method can produce a reading within a few minutes.

But identifying people with HIV within a few days or weeks of infection has become a public health imperative, in part because the virus level tends to be highest during the early infection stage — making transmission to others more likely, she said.

“This really is a key to preventing HIV transmission,” Johnston said.

Because of the blood test’s cost, health experts said, it probably isn’t practical to offer the higher-level screening to the general population. It makes more sense to focus on high-risk HIV groups because they record larger numbers of false-negative antibody test results.

In the San Diego study, participants were recruited from several HIV testing sites in the region, including those run by UCSD, the county and the Lesbian, Gay, Bisexual, Transgender Community Center .

Each participant was given the saliva swab test, and then blood samples were taken from those who tested negative. The samples were sent to labs in San Diego and Emeryville in the Bay Area, where they were analyzed for HIV nucleic acid. Patients who tested positive for HIV after the blood analysis received the results from clinic staffers within a week.

Morris said the blood test is sensitive enough to detect the virus components within 10 days of infection.

“I think the time is coming where we will have to adopt a strategy for earlier (HIV) detection,” he said. “If you have a testing site with a high-risk prevalence, then you probably should be running this test on all of their samples” that tested negative for virus antibodies.

Keith Darcé: (619) 293-1020; keith.darce@uniontrib.com

 

FDA seeks to ban Chicago HIV doctor from research

Regulators say his clinic submitted phony data, forms with forged signatures

June 14, 2010|By Patricia Callahan, Tribune reporter

In a rare move, federal regulators are seeking to disqualify a prominent Chicago HIV doctor from future drug studies after they discovered his clinic committed one of the most grievous sins of medical research: submitting fictitious data in a drug trial.

The Food and Drug Administration said Dr. Daniel Berger "failed to protect the rights, safety and welfare" of patients under his care.

Doctors' and patients' signatures were forged, even on forms where patients said they understood the risks of the trial and those where doctors said the patients weren't too sick to enroll, the FDA found.

 


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