An Interview With Jeffrey Martin, M.D., M.P.H.
Somebody brought up IRIS [immune reconstitution inflammatory syndrome] and it seems like you were glad that they did. What's the connection between KS and IRIS?
IRIS is a condition where, after you give someone antiretroviral therapy, whatever disease complication of HIV they may have -- TB [tuberculosis], cryptococcal disease -- it paradoxically gets worse. That's thought to be because, when the immune system improves, it shows its new strength by attacking many foreign antigens you might have in your body, causing various kinds of HIV-related disease manifestations. So, for several years now, when patients got antiretroviral therapy and their KS got worse, it was thought to be attributed to this thing called IRIS.
But, in fact, I think it's a complicated story with KS. A lot of the KS that gets worse after you give antiretroviral therapy may just be the natural history of KS, which we know over time will get worse. So, distinguishing that natural history from this inflammatory-induced disease caused by immune reconstitution, I think, is difficult, if not impossible, just by clinical appearance. We're going to need really sophisticated laboratory tests to sort it out.
Now, the reason it's important to sort this out is that the IRIS may get better on its own, as the immune system calms down. We see this with other conditions. [For] people who have IRIS-induced worsening, you might want to do nothing but just conservative management; things will get OK. But [for] the KS that worsens because of natural progression of disease, if you don't intervene, the patient could continue to get worse, beyond the point where any additional therapy will help. So, distinguishing the origins of these two forms of worsening of KS (IRIS versus natural history) is a very important research objective going forward.
Based on what you found in your study in Africa, what would be one implication for practice that you'd want to share with practicing clinicans regardless of where they're practicing?
On the basis of these data, for treating people with established KS in Africa, we do not find a benefit for use of a protease inhibitor-based regimen. The fact that we found that in Africa may have similar implications for practice in the U.S., but this is just speculation.
Equally important, though, is that antiretroviral therapy alone is, in many cases, not going to be sufficient for treatment of KS. Therefore, any patients with KS who are given ART alone need to be followed very closely.
This transcript has been edited for clarity.
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