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A Common Blood Product Called IVIG May Help Clear the HIV Reservoir

By Alan McCord

February 23, 2009

During an oral presentation at CROI 2009 in Montreal, Canada, Dr. Magnus Gisslen detailed early findings from a small proof-of-concept study using high-dose intravenous (in the vein) immunoglobulin (IVIG) to reduce the amount of HIV found in cells where HIV quietly lurks, sometimes call the latent reservoir. These reservoirs are compartments of HIV infection, seemingly untouched by conventional HIV therapy, that are believed to harbor the virus that eventually causes people to progress in their HIV disease.

This year, CROI participants were privy to a great deal of information regarding the activation of inactive or quiet HIV-infected immune cells. Much of the data are results from discovery studies trying to remove or otherwise activate the virus from these rather stable cells, in hopes of treating HIV disease or eradicating the virus altogether. Although this IVIG study may not provide a therapy in the short-term, it's one example of the wide breadth of study that's currently being done, in attempts to find ways to remove HIV from these stubborn resting cells of infection.

IVIG contains immunoglobulins, or antibodies, that are given intravenously. IVIG does a variety of things, including changing the way immune cells communicate in order to activate other immune cells. It's approved by the FDA for treating various conditions including Kawasaki's Syndrome or Guillain-Barre Syndrome. The therapy is made from the plasma of hundreds of blood donors.

The basis for this small study came from observing a patient who had been on potent HIV therapy and then was given IVIG to treat Guillain-Barre Syndrome. The IVIG therapy was successful and was stopped, after which the individual went on to stop his HIV meds as well. His viral load stayed undetectable for several months after stopping his HIV regimen, with a return in detectable virus in blood at 7 months. Although this is not unheard of, it did give researchers pause to consider that IVIG may have impacted this person's latent HIV. A small study was constructed to examine this more closely.

The small study enrolled nine people on effective HIV therapy for five or more years who had undetectable viral loads for more than 1.5 years. They were given 30g IVIG daily for five days. Lab work, which included identifying the genetic types of HIV in latent reservoirs and blood, was done before and after the IVIG therapy. Seven out of the nine showed lowered or undetectable virus particles in these reservoirs 8 to 12 weeks after the IVIG therapy. On average, latent HIV was reduced by 68% in the 7 patients who showed a response to the IVIG.

Small rebounds, or blips, of viral load occurred after the IVIG doses, which may be due to the IVIG activating latent HIV. The genetic types of the latent HIV before the IVIG doses were compared to the virus found in the blood during the viral blips after the doses of IVIG. The types of HIV were similar enough to suggest that the virus in blood was indeed from these reservoirs.

The mechanism that reduced the latent HIV for this short time is unknown. These findings need to be reproduced and expanded upon to more fully understand what's going on.

Whether IVIG could be used to treat HIV infection, it would come with major challenges. First, it's very expensive. At the doses needed, it would be a costly therapy even under the best of circumstances. Second, it's in very small supply. Should it prove effective, large-scale production would be a major hurdle to overcome. Third, it must be given through a needle in the vein (intravenously), daily, which would make it undesirable for many people. However, should this concept prove useful, it could lead to developing less costly versions of the therapy that are perhaps less difficult to administer. It was this sort of clinical data on latently infected cells that raised the curiosity of many of this year's attendees.

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