March 25, 2014
To many, the condition known as Kaposi's sarcoma (KS) may feel like a relic from the HIV epidemic's bygone days. But in many parts of the world, KS remains as clear and present a health danger today as it was in the U.S. in the 1980s and 1990s, when American society considered it one of the primary markers of AIDS. Additionally, though the historical impact of KS on people living with HIV is tremendous, there remains a great deal we don't know about the disease.
However, a flurry of newly presented and published research seeks to peel away the remaining curtains that block a more complete understanding of KS epidemiology and treatment. At this year's CROI, an annual HIV research conference that recently took place in Boston, a full discussion session was devoted to the topic. Our correspondent Terri Wilder spoke with one of the session presenters, Jeffrey Martin, M.D., M.P.H., a professor in the division of clinical epidemiology at the University of California-San Francisco, about his research and other recent developments in the field.
I'm curious as to why you think CROI decided that this was an important topic, when some clinicians just don't see it that often. Folks saw it in the '80s, of course, and '90s, but many aren't seeing as much anymore.
Indeed: In the U.S., KS incidence has dropped precipitously, and that's because virtually all people with HIV are getting treated. In sub-Saharan Africa, though, it's a completely different story.
Most of the presentations today were about sub-Saharan Africa where, most people are surprised to hear, KS actually is, according to 2012 statistics, the second most-common cancer in the entire general population. It's not just an oddity confined to HIV-infected patients; it's ... second only to cervical cancer in its frequency in the general population. So I think that's why the organizers want to bring some focus to it.
In particular, not only is it common, but it's also orphaned, in terms of who is taking responsibility for it from a research and clinical perspective. It's falling in between the cancer doctors and the HIV doctors. That's led to it not getting the clinical respect it needs. For example, in Africa, we're using the chemotherapy that we used in the 1970s in the U.S. and Europe.
I think the organizers, and particularly myself, want to actually bring some hard data to the situation to bring KS to the attention of policymakers, governments and ministries of health, to get standards of practice for KS up to where they are in the U.S., such that someday we can say KS is gone in Africa. But we're a long way away from there.
Tell me a little bit about your study that you talked about today.
This study [download poster PDF] was one where we used two common forms of antiretroviral therapy -- one containing protease inhibitors and one not -- to see if one ... was better in treating people with KS.
We've known for some time that a lot of people who get ART [antiretroviral therapy] alone for KS will have their lesions melt away. In fact, that was one of the big triumphs when ART first came out. But we've never really known if there was a specific kind of antiretroviral regimen that had a better effect than others. There are so many ART drugs: Does one regimen have any particular strong effects against KS?
A lot of people, for several years now, have felt that protease inhibitors did have special unique properties against KS. So we formally tested this in our randomized trial.
In short, we did not show that protease inhibitors had a benefit on overall survival in people with KS; the protease inhibitor did not do better than a non-protease inhibitor-based regimen.
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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