High-Dose Intravenous Immunoglobulin May Reduce Latent HIV Reservoir

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A Discussion With Magnus Gisslén, M.D., Ph.D.
February 10, 2009

Magnus Gisslén: The viral reservoir in latent, HIV-infected CD4+ cells is very stable and has a very long half-life. As yet, no approach to decrease this reservoir has proven effective.

We looked at intravenous immunoglobulin [IVIG] given in high dosage together with effective antiretroviral therapy [ART] to see how it interacts with this reservoir.1 The idea was raised from one patient of mine that has Guillain-Barré syndrome [GBS], which is treated with intravenous immunoglobulin. He had treatment with ART and immunoglobulin at the same time. Subsequently, he decided to stop his ART due to different reasons; mainly, that he wanted to do so. His viral load stayed below 50 copies/mL for several months, which is rather uncommon, although it can happen sometimes. That led us to the hypothesis that the immunoglobulin might have had some effect.


Magnus Gisslén, M.D., Ph.D.
We tried to test this hypothesis with a small pilot study where we included nine subjects, all with effective treatment with an HIV RNA less than 50 copies for at least 1.5 years. They took their antiretrovirals with immunoglobulin for five consecutive days -- 30 grams of immunoglobulin each day.

We looked at the HIV-infected units per million resting cells before and after the treatment with immunoglobulin. That was replication-competent virus [RCV]. We found that there was a decrease of RCV in the majority of patients.

In seven patients, we had the possibility to evaluate because we could detect virus in the reservoir. Of those, five decreased [in RCV]. They decreased by 68% or more in this reservoir, until we couldn't find any change from baseline to follow-up.

Also, we found that during or shortly after they got their immunoglobulin therapy, they had a small viral load increase in plasma -- up to 10, 15, 20 copies/mL of blood. The magnitude of this increase was closely related to the amount of virus in the reservoir at baseline. Also, there was a relationship found when we sequenced virus from plasma and the reservoir. It looks like the virus in plasma came from the reservoir.

Together, it looks like somehow the HIV reservoir is affected by intravenous immunoglobulin. Intravenous immunoglobulin has several effects on the immune system: It acts on the cellular level, on the Fc receptor and on cytokines. So it has a lot of different, complex modes of action. And actually, we don't know the mechanism. We found that IL-7 [interleukin-7] increased in all cases from baseline to day eight, but we don't know why this looks like it works.

But this was a small study, of course; it has to be replicated and extended in larger studies.

MORE:

http://www.thebody.com/content/confs/croi2009/art51696.html?ic=700100