Gilead Following Multiple Paths Toward HIV “Functional Cure”

3/24/14Follow @tanseyverse

The first researchers who tried to stop the AIDS epidemic in the 1980s were faced with a terrifying virus that invaded key cells of the immune system, forced them to make many copies of itself, and burst the cells open in the process, leaving the human host defenseless against an onslaught of HIV and other infections.

Looking back on that drive to find the first HIV drugs, the task seems relatively simple to Romas Geleziunas—at least, compared to the problem he’s tackling now.

Geleziunas, director of clinical virology at Foster City, CA-based Gilead Sciences, is trying to thwart a second, more insidious way the HIV virus invades cells. Early in the course of infection, the virus inserts itself into the genome of immune system cells, but without either copying itself or killing the cell. The cell and the virus then wait together in a kind of slumber. But they can later awaken to unleash a new generation of infectious virus particles.

This reservoir of latently infected cells is now seen as the barrier standing in the way of a longed-for cure that could free HIV-positive individuals from a lifetime of taking the antiretroviral drugs developed by Gilead and other companies since the late 1980s. Those drugs protect uninfected cells, drive down blood levels of the virus, and stave off full-blown AIDS. But they don’t eliminate the HIV reservoir, which appears to be complex and pretty mysterious.

“We don’t fully understand what are the reservoirs that harbor HIV,” Geleziunas says. “That makes the mission very, very tough.”

Gilead, the world’s largest maker of antiretroviral drugs, began its search for ways to eradicate the HIV virus from the body about five years ago, Geleziunas says. He’s ready for the natural question that follows: Why would Gilead push hard to eliminate the need for its own HIV drugs, which bring in about $9 billion in annual revenue, and which can change a deadly disease into a chronic condition managed by a single daily pill?

Geleziunas says the answer is simple: the company knows that patients would rather be released from the need for any HIV medicines. Gilead is on the hunt for next-generation HIV therapies it can commercialize that would wipe out the virus—hopefully for good—after a limited time on treatment.  “We were one of the first companies into the field,” he says.

The company doesn’t use the freighted word “cure” to describe its goal. “We prefer to say we want to create a state of HIV remission that could be controlled without drugs,” Geleziunas says.

Gilead has been exploring a range of different strategies to block the HIV virus from surging back after treatment, and has been lining up research partnerships that include other drug developers, academic researchers, and government agencies.

“We’ve created a hub for clinical and basic research,” he says.

Gilead’s efforts are part of a larger research mobilization that has been galvanized by recent reports about a few HIV-positive patients who have actually been able to stop their drug regimens—though they did this after treatments that might be difficult to extend to large numbers of patients. For example, the HIV-positive “Berlin patient,” whose case was reported in March 2011 in the scientific journal Blood by a research team at Charite´-University Medicine Berlin, in Berlin Germany, received a bone marrow transplant for his leukemia from a donor who happened to be one of the rare individuals with a natural genetic immunity to HIV.

Even so, scientists pursuing a “functional cure” for HIV have been emboldened by the Berlin patient and other cases, says Dr. Warner Greene, director of the Gladstone Institute of Virology and Immunology in San Francisco.

“The anecdotal cases suggest that we’re not tilting at windmills,” says Greene, a top HIV expert.

Greene sees an urgent need for a cure. Patients taking long-term antiretroviral drug regimens are still vulnerable to the premature onset of diseases of aging. Across the globe, about 35 million people are infected with HIV. (About the same number have died.) The cost of maintaining patients on lifetime therapy is a significant burden even for developed countries, while the drugs are inaccessible to millions of infected people in Africa and other regions, Greene says.

“Sixteen million people are not receiving it, and they’re dying,” he says.

Greene points to gene therapy as one of the major strategies being pursued to achieve a functional cure. Richmond, CA-based Sangamo Biosciences (NASDAQ: SGMO) recently showed progress in its drive to modify the genes of HIV- positive patients and replicate the immunity that the “Berlin patient” acquired from his bone marrow donor.

Greene says he values Sangamo’s work, but he expects that most of the world’s HIV-positive population won’t be able to pay for Sangamo’s multi-step procedure to modify the genes in blood cells of individual patients. To achieve global eradication of HIV, researchers will have to develop simpler treatments that can be scaled up for mass populations, Greene says.

That may mean devising a drug, or drug combination, that depletes the HIV reservoir in latently infected cells. And the task doesn’t look easy so far, Greene says.

“It’s a bigger, nastier problem than we thought,” he says.

Scientists had optimistically predicted in the mid-1990s that … Next Page »

Bernadette Tansey is a freelance journalist based in Berkeley, CA. Follow @tanseyverse

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  • jack

    They don’t do nothing, a lot of criticism is have with pharma so he tried to save ,i don’t think they really do for cure.

    • holiday

      HIV treatment interruption on horizon, pro140 could alleviate patient symptoms and save $$ eating into big G’s $9 billion annual HIV revenue

  • http://www.herpeswoo.com/ HerpesWoo.com

    The company doesn’t use the freighted word “cure” to describe its goal.

  • apostleshadamishe

    AMBUSH CURES HIV/AIDS

    Apostle Shada Mishe

    apostleshadamishe@gmail.com

    Sir / Madam,

    For the past 12 years I have been studying and researching Ambush, a Palm plant extract that is effective in curing HIV.

    Name of Plant; Palm

    Name of ingredient: Ambush

    Molecular weight 640 (similar to the sequisulfides)

    Where found: In and around the areas of South Florida where uranium waste was dumped in the 1920′s from the nuclear programme that has now leaked out into the water system. A specie of the PALM plant has picked up this waste to be the valuable AMBUSH.

    Chemical compd; Uranium isotope (cus.n) Grayish white soft metallic compound NOT found in chemistry books.

    Uses: Antiviral DRUG..Ambush

    Found to “KILL” the HIV virus when given in a dose of 60 ml three times daily for 21 days at a known concentration.

    Mode of action.. Ambush kills the HIV virus by causing the viral shell to rupture . In the lymph system Ambush produces “natural radioactivity” that “kills” the virus that ‘hides’ in the lymph system . This crosses the blood-brain barrier since the ‘patients’ claim that they are able to see,hear and think more clearly after taking Ambush.

    Viral Loads…This decreases from 100,000 to ‘undetectable’ in 21 days….. but I have had patients VL go to ‘undetectable ‘ in 5 days.

    SIDE EFFECTS / EFFECTS
    1. After 5 to 7 days of treatment, patients MAY complain of HEADACHES.
    2. After 5 to 7 days male patients experience an increase in erection.
    3. Stool becomes soft and REGULAR
    4. Patients c/o being WARM in the trunk area mainly at night when lying down.

    Toxicology……Before administering to any person a complete toxicological analysis was done to include, arsenic, barbiturates and NO KNOWN poisons or harmful substances to mankind were found.

    Systems/Organs

    Skin…becomes clean, smooth and free of eczema or other say they have small eczema patches in the first week that go away by the third week.

    Excretion
    Since this is a very LARGE molecule it is excreted relatively unchanged via urine and feces.

    SEROREVERSION
    After 149 days the patents revert to being HIV NEGATIVE after finishing a course in Ambush hence no one goes public to say they WERE HIV positive.

    Pharmacology of Ambush on the GUT of an end stage AIDS person.

    It is known that late stage AIDS patients posses a high level of the virus in the GUT which should include the entire GI tract from stomach to rectum. Here the virus is found in the lining and this is difficult for ARV’s because these are the areas needed by the ARV’s to enter the blood supply. There is not a high enough blood level returning back to the stomach lining hence the virus remains in high concentration.

    This causes the person’s appetite to decrease which causes a spiraling downhill of the body.

    When Ambush is taken in the liquid form, it is slightly basic and forms a stable compound in the acidic stomach.The Ambush compound is close to the stomach lining to exert the “natural radioactivity” effect which kills the virus in the stomach. Here the entire mid section feels very warm and sometimes feverish. The infected stomach lining with the dead areas is then passed out as a black slime in the stool. This usually happens about day 4 while on an Ambush regime of 60 ml three times daily for 21 days, wherein the person has a large bowel movement.

    After the bowel movement, the person becomes extremely hungry and eats TWO to THREE times a normal serving. Here I usually recommend cornmeal porridge with butter or cooking oil as a prevention against malnutrition and add a daily multivitamin. By day 10 the stomach has recovered and the person eats normally.

    THE CHALLENGE

    The challenge is to find a Virologist, or Biologist of HIV Researcher who is willing to put some Ambush in a Human culture medium infected with the HIV virus, incubate with proper controls and report their findings to the world.

    More info is at http://www.ambushcuresaidsfree.com or
    http://www.youtube.com/user/apostlemishe?feature=mhee

    Thank you for your interest and we will be happy to send you samples and answer any and all questions.

    Apostle Shada Mishe
    apostleshadamishe@gmail.com
    Dallas Texas,
    1-972 294 5161

  • jack

    It statements just for answers of alot of criticism .. said still they don’t want cure…anyhow e wants to keep sale more druge…this way more people will die…

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  • matija

    latent cells were found earlier than 1995 and in individuals already at seroconversion…it is very difficult to see how the CMV vaccine could eliminate these cells, as they express no viral proteins (possibly these studies did not wait long enough)…in addition, your article avoids transcriptional interference, where the virus is silenced by host cell transcription across its genome, a rather difficult situation to overcome…finally, romidepsin will have no effect on completely resting cells…it is good to understand a bit about the host cell transcription and viral integration…

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  • Jack Allen

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  • patrick stella

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    have it in mind that he can’t cure HIV I just decided to give a try I
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    and some question about me I give him all the detail he needed and I
    wait to see his reply to my problem after all the things is done he ask
    me to go for check up I went for hiv test I cant believe I was negative
    the midical doctor was surprasie and doctor even ask for dr ,cuba email
    which i give to him, he he is help people that contact him also he can
    still help you on your cure thanks dr.cuba for helping me for the cure
    at this young age if you need help contact him now
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