Starting HIV Drugs Earlier May Delay AIDS But Not Death

New research suggests that HIV-infected patients are most likely to stay clear of AIDS longer if they start drug therapy when their immune systems are still relatively strong. However, starting treatment earlier, compared to waiting, didn't affect dying from AIDS. "There wasn't a clear benefit in terms of preventing death" by prescribing the drugs before some guidelines suggest, said Dr. Keith Henry, director of HIV clinical research at Hennepin County Medical Center in Minneapolis and co-author of a commentary accompanying the study, published in the April 19 edition of Annals of Internal Medicine.

The issue of when to begin drug treatment is a hot topic in the field of AIDS/HIV medicine. If physicians wait to begin treatment, patients can delay the expense not to mention the side effects of pricey anti-HIV drugs. But such delays may also give the virus a chance to become more powerful and better able to fend off medications. If they're not treated with drugs, HIV-infected people almost always go on to develop AIDS. So when should doctors turn to the drugs? In the U.S., guidelines suggest that HIV-infected patients take them when the level of CD4 cells an important part of the immune system dips below 0.500 X 109 cells per liter (cells/L).

In Europe, the guideline number is frequently lower meaning a weaker immune system at under 0.350 X 109 cells/L.In the new study, researchers examined how patients did when they began drug therapy with their CD4 cells at a variety of levels. The study authors examined the medical records of almost 21,000 HIV-infected patients who sought treatment in HIV clinics in Europe and through the Veterans Health Administration system in the United States. The researchers found that the death rate was about the same regardless of whether patients began treatment when their CD4 levels dipped under 0.500 X 109 cells/L or if they waited until their immune systems deteriorated more and reached below the level of 0.350 X 109 cells/L.

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Tissue Analysis May Help Predict Breast Cancer Outcome

An analysis of breast tissue may help doctors better predict outcomes for women with breast cancer, a new study reports. Researchers analyzed what they describe as "highways" of connective tissue in breast cancer tumors, and found that the way collagen fibers the main component of connective tissue are arranged may aid in a patient's diagnosis and help determine treatment. Collagen not only surrounds most body organs and helps provide structure for the body, it also tells cells how to behave, the study authors noted. Normally, a close-up of collagen resembles a jumbled path or a plate of cooked spaghetti.

In the new study, the researchers analyzed tumor cells from 200 patients with invasive breast cancer. The investigators found signs that the collagen began to act differently as the tumors progressed. "We think the cancer cells start to pull on the collagen and straighten it out, forming a track or highway on which the cells can migrate," study senior author Patricia Keely, an associate professor of cell and regenerative biology at the University of Wisconsin-Madison School of Medicine and Public Health, said in a university news release. As the highways became more developed, the prognoses for patients worsened, the study found.

"We have identified a novel collagen-signature system that may become a very useful addition to the tools clinicians use to determine a breast cancer patient's prognosis," Keely explained. The research is published in the March issue of the American Journal of Pathology. Commenting on the study, Dr. Priscilla A. Furth, a professor of oncology and medicine at Georgetown University's Lombardi Comprehensive Cancer Center, described it as an example of "valid basic research." However, "before any new prognostic test can go into practice it must be extensively validated. This publication is a first step that might trigger additional research to examine the utility of this type of analysis in different settings and by different groups," said Furth, who was not involved with the study.

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Gene Therapy Against HIV Not a Proven Cure

Experts are reacting with cautious optimism to the announcement Monday that researchers reconfigured immune cells so that they became resistant to HIV in six patients infected with the virus. But they say the jury is out on whether the technique might ever spell an end to AIDS. The goal is ultimately a cure or what's called a "functional cure" having the body permanently keep HIV at bay but "we're not there yet," stressed Dr. Michael Kolber, professor of medicine and director of the Comprehensive AIDS Program at the University of Miami Miller School of Medicine.

The trial, reported Feb. 28 at a meeting of HIV specialists in Boston, "was a proof-of-principle that they could go in and do this. They demonstrated that the cells stayed in the patients, but the patients were not cured," said Kolber, who was not involved in the new research. Another expert agreed that the treatment's true potential remains uncertain. "If successful, this probably could have wide application, but going from six patients to an entire epidemic is a ways to go," said Dr. Michael Horberg, director of HIV/AIDS at Kaiser Permanente Health Plan and vice chair of the HIV Medicine Association.

"With other successes we've already had, that makes it more promising and people are starting to have a greater vision as to what's possible." However, as Kolber pointed out, this trial was what's known as a phase I trial, which means it was primarily looking at safety, not effectiveness, although investigators do often report on initial effectiveness results at this stage. The idea came from an isolated case that first made headlines in 2009, involving the so-called "Berlin patient." This man, an American AIDS patient living in Germany, was apparently cured after receiving blood cells from a donor who happened to have a rare, natural immunity to HIV.

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New Drug Strategy Shows Promise Against HIV

Scientists are reporting early but promising results from a new drug that blocks HIV as it attempts to invade human cells. The approach differs from most current antiretroviral therapy, which tries to limit the virus only after it has gained entry to cells. The medication, called VIR-576 for now, is still in the early phases of development. But researchers say that if it is successful, it might also circumvent the drug resistance that can undermine standard therapy, according to a report published Dec. 22 in Science Translational Medicine.

The new approach is an attractive one for a number of reasons, said Dr. Michael Horberg, director of HIV/AIDS for Kaiser Permanente in Santa Clara, Calif. "Theoretically it should have fewer side effects and there's probably less of a chance of mutation in developing resistance to medication," said Horberg, who was not involved in the study. Viruses replicate inside cells and scientists have long known that this is when they tend to mutate potentially developing new ways to resist drugs. "It's generally accepted that it's harder for a virus to mutate outside cell walls," Horberg explained.

The new drug focuses on HIV at this pre-invasion stage. "VIR-576 targets a part of the virus that is different from that targeted by all other HIV-1 inhibitors," explained study co-author Frank Kirchhoff, a professor at the Institute of Molecular Virology, University Hospital of Ulm in Ulm, Germany, who, along with several other researchers, holds a patent on the new medication. The target is the gp41 fusion peptide of HIV, the "sticky" end of the virus's outer membrane, which "shoots like a 'harpoon'" into the body's cells, the authors said. The launch of this peptide is a first step in the virus's bid to inhabit host cells.

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Docs Claim Transplant Cured Man of HIV, But Experts Urge Caution

In a rare case, a man living in Germany who had both leukemia and AIDS no longer has any detectable HIV cells in his blood following a stem cell transplant for his leukemia three years ago. But experts were quick to caution that the case does not have practical implications for the treatment of AIDS worldwide. As it turns out, the donor for that transplant carried a rare mutation in a gene that increases immunity against the most common form of HIV.

First reported in 2009, this follow-up study, published online in the journal Blood, confirms that the recipient patient is still free of both leukemia and HIV three years after the transplant. But one expert issued strong words of caution in interpreting the finding. "Our phones have been ringing off the hook," said Dr. Margaret Fischl, director of the AIDS clinical research unit at the University of Miami Miller School of Medicine. "We are having patients calling us and asking if they can stop their antiretroviral therapy and the answer is uncategorically no."

The theory is that if you could wipe out every infected cell you could cure HIV, Fischl said, but this is a unique case. The patient had intense chemotherapy and radiation, then relapsed and was given a second transplant from the same donor. The donor was unique in that he had a gene that could fight the most common form of HIV. This mutation is seen in about one in every million people, Fischl explained.

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Researchers Turn Stem Cells Into Intestinal Tissue in Lab

Researchers say they've turned human stem cells into functioning human intestinal tissue in a laboratory setting. The study team described its accomplishment as a "significant step" forward in efforts to better understand the function and development of the human intestine. They also expressed hope that the innovation will spur the development of new strategies to combat intestinal diseases, while opening up new avenues for the generation of transplantation tissue.

"The hope is that our ability to turn stem cells into intestinal tissue will eventually be therapeutically beneficial for people with diseases such as necrotizing enterocolitis, inflammatory bowel disease and short bowel syndromes," explained study senior author James Wells, a researcher in the division of developmental biology at Cincinnati Children's Hospital Medical Center, in a hospital news release. Wells and his colleagues report their findings in the Dec. 12 online issue of Nature.

The authors used two types of so-called "pluripotent" stem cells -- cells that have the chameleon-like ability to differentiate into any one of about 200 distinct cell types. Human embryonic stem cells, which are known to have such transformative abilities, were one type. For the other, the researchers looked to "induced" stem cells cells harvested from patients and reprogrammed in the lab to function as pluripotent stem cells. Though less well-tested than embryonic stem cells, induced cells theoretically have the advantage of minimizing the risk for cell rejection when replanted back into the host patient.

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