HIV Management In Depth

Can Antiretrovirals Help Those Who Control HIV Naturally?

An Interview With Jonathan Li, M.D.

March 11, 2014

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Do you guys have a hypothesis going in that led you to use Complera as your drug of choice? Is there anything in particular you're expecting?

Yeah. One of the reasons we chose Complera is that it's better tolerated than efavirenz, which is the most commonly used antiretroviral therapy today -- Atripla; efavirenz-based or containing regimens. But rilpivirine (Edurant) has been shown to be better tolerated. Now, in a head-to-head trial against efavirenz, rilpivirine did worse in the group of patients with the highest viral load -- those patients with viral load over 100,000. [But our] patients are the exact opposite of that; these are patients with the lowest viral loads. Those patients did really well in that study.

That is one of the reasons why Complera was chosen. But our hypothesis is that antiretroviral therapy will decrease not just T-cell inflammation, but also a lot of these soluble markers of inflammation that you've been hearing about that have been linked to various other chronic, long-term effects of aging and non-AIDS-defining conditions -- cardiovascular disease, cognitive dysfunction and things like that.


I think that another important point is that I've been asked: What does this mean for the cure agenda?

HIV controllers have always thought to be an ideal, natural model for what a successful functional cure would resemble. If you can get someone who is not a controller to a controller status by stimulating their immune system, or somehow giving them some therapeutic vaccine, that would be as good as a cure.

But if this is really our goal, then I think that we have to have a complete understanding of what it means for our patients. Will further suppression of this already low-level viral load have any additional benefits for our patients, for this population -- and for our patients in the future? What is the cost of not achieving complete suppression of the virus?

And by "complete," in this case you're talking about, what? Sub-10 viral load? Sub-5?

You can't give a number to it. Because even when patients are on a fully suppressive antiretroviral therapy regimen, if they're a hundred percent adherent, you can still find some HIV in their bloodstream. How much HIV is in there will depend on how long they've been on treatment, and probably depend on kind of the size of their viral reservoir, things like that.

But that HIV is not likely to be causing new rounds of replication. Some of that is just some HIV that will come out because they've got this reservoir where HIV is constantly being produced.

But HIV controllers -- elite controllers and controllers -- will have higher levels. It's hard to quantify the difference. But it's been shown that HIV -- even elite controllers have these detectable viremia episodes, and controllers have even higher viral loads than that. These are definitely higher viral loads than what you would normally see, I think, in patients on long-term suppressive antiretroviral therapy.

The question is, does getting them from an already-low level to fully suppressing them to an even lower level: How much does that help? And do we think that that amount of benefit, in terms of inflammation, is enough to affect any downstream long-term health of these patients?

Also, I think the immunology and virology components of the study will give us a lot of important insight on the pathogenesis of HIV within this population, and really give us a deeper understanding of where HIV is hiding, and how the immune system maintains control. When we're studying elite controllers, and we say, "OK; so controllers have some amount of viral replications. And we know that controllers have higher amounts of chronic inflammation." Well, are these two related? If you don't treat, you can never 100 percent tell how much these things are related, or whether they are two completely different processes.

Those are some of the reasons behind doing this study -- in addition to just helping the patients themselves.

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This article was provided by TheBodyPRO. It is a part of the publication HIV Management in Depth.


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