This Month in HIV: Breaking HIV/AIDS Research From CROI 2007
Dr. Gallant and his colleague, the noted HIV researcher, John Bartlett, are coauthors of Medical Management of HIV Infection, a respected, annually updated clinical guide. Welcome to This Month in HIV, Dr. Gallant.
Thank you, Bonnie. It's good to be here.
Dr. Gallant, this podcast will focus on the latest research from the 14th Conference on Retroviruses and Opportunistic Infections which as you know took place at the end of February in Los Angeles. For our listeners who do not know about this conference, The Retrovirus Conference, which is also known as CROI, is the most important HIV/AIDS research conference of the year. Knowledge about HIV is incremental. Researchers and clinicians attend these conferences hoping to learn more about how to optimally treat HIV. But with 1,000 studies presented, it's a challenge to figure out which studies were most impactful and actually will change practice. I thought you might be able to help our listeners understand results of some of the studies that were presented.
The first question I had was related to first line, or initial, HIV therapy. Do you think we've come closer to knowing when it's optimal to start HIV therapy?
I think we're at the point now where a more interesting question is: When should you not treat somebody? I think we're clearly getting to the point where we need to be treating people [with HIV] earlier than we do now. Lots of studies from different cohorts [clinical trial groups] have shown that there are benefits to treatment at almost any stage of HIV infection. The SMART study, where they randomized people to either stop therapy or continue it, is showing us that people who are not on treatment are having problems that we wouldn't typically attribute to HIV -- problems like heart attacks and kidney problems and liver problems. [To read more about structured treatment interruption and the SMART study, click here.]
"I think we're at the point now where a more interesting question is: When should you not treat somebody?"
So for me, the more interesting question is: Who would I not treat? The only people that I can think of that I would not consider treating would be long-term nonprogressors, or people who might be long-term nonprogressors, or people who are unlikely to take their medication. Short of that, I think virtually anybody is a candidate for therapy. When we have such effective therapy against an otherwise fatal disease and the therapy has so few long-term toxicities, I think it makes sense to be more aggressive.
What does "more aggressive" mean to you? If I have a CD4 count of 500, would you start me on therapy?
"... starting [HIV treatment] earlier is better from all different kinds of standpoints, including better CD4 responses, fewer opportunistic complications, fewer non-opportunistic complications, and ultimately, possibly better survival and better health."
It's never a question of me starting somebody [on HIV treatment]. It's a question of me talking to somebody about whether they want to start [on treatment]. I think if you had a CD4 count of 500, but you had a high viral load and there was evidence that your CD4 count was decreasing, I would at least talk to you about being treated. Because the [U.S. government treatment] guidelines don't say that [HIV treatment should be started in people with CD4 counts of 500] -- the guidelines currently say 350 -- I wouldn't push this too much [Click here to view a PDF of the U.S. treatment guidelines.]. If somebody said, "I don't really want to be treated yet; I'd rather wait till I have to," I wouldn't push the issue. But I do point out to patients that the guidelines are almost certainly going to change soon, and will almost certainly become more aggressive than they are now. I talk to them about the data showing that starting earlier is better from all different kinds of standpoints, including better CD4 responses, fewer opportunistic complications, fewer non-opportunistic complications and, ultimately, possibly better survival and better health. So I think we're getting to that point.
Are you saying that we may eventually recommended that people start treatment at any CD4 count? It's no longer 350. I know people are hanging their hat on 350.
No, we shouldn't. You know, that number is going to change soon. Don't get too fixated on 350. Dr. Mellors presented data from the MACS cohort, and then there was also data presented from the ALIVE [AIDS Link to Intravenous Experience] cohort at [Johns] Hopkins [University], showing that, in fact, the viral load is a much better predictor of progression to AIDS or death than the CD4 count is. We've kind of been ignoring the viral load recently when we make decisions about when to start. Maybe that was a mistake.
So, in terms of something related to first line primary infection: a lot of people who know -- I know there's just a very small population of people who know that they have just recently become infected, who get treatment. Do we know whether HIV treatment at that point is beneficial?
I wish I could say I knew the answer. The data presented at this conference, and at all the other conferences I've seen, have been very conflicting. You know, there's some data suggesting that it's a good idea; others not clearly making that point. I think we still don't know the answer.
I think if there's a group of people where I would be most likely to urge treatment, it would be people who are diagnosed very early, before they have even sero-converted -- when they are in the middle of the acute retroviral syndrome. I think there are some data to suggest that treating people at that point may help, in terms of reducing [viral] set point and reducing the loss of some of your CD4 cells in the intestinal tract that clearly disappear quickly with infection.
I think our uncertainty is why it's so important to diagnose people at this stage and get them into clinical trials. Because there are studies ongoing where we're comparing treatment versus no treatment [during acute or primary infection], to find out whether there's any benefit. We really need to be making these diagnoses [during acute infection]. It drives me nuts when I see people who had risk factors, went into a hospital, had a fever, and the doctor thought about mono, and the doctor thought about flu, but never thought about acute HIV and never did the right tests.
Would you describe acute HIV symptoms as resembling flu symptoms?
Yes. They are like flu or mono -- fever, maybe a rash, maybe swollen lymph nodes, fatigue. They're pretty non-specific; they could be symptoms of a lot of things. But I think the point is, if you're a physician and it crosses your mind that somebody could have mono then it should also cross your mind that they could have acute HIV, because the symptoms are identical. There's just no way you can think of one and rule out the other on the basis of symptoms.
What's the good thing about reducing one's set point? And could you clarify what that means?
Well, if it's true that you would reduce the set point, what it would mean is that, if you were to stop therapy after acute infection, you would have a lower baseline viral load than you would have had, had you not been treated. Therefore, presumably you might progress slower and not need to be restarted on therapy for a much longer period of time. Now, that has not been clearly shown, but that's the idea.
So we still don't know that much, I guess.
We still don't know. The reason we don't know is because so few people get diagnosed at this stage. That's a problem with medical care.
Okay, on to my next question. Resistance tests: Do we know if transmitted HIV drug resistance is on the rise? Is there any more proof of this?
If you look at the United States, it has been on the rise over the second half of the last decade, and the first half of this decade. It's sort of steadily been rising. In most of the rest of the industrialized world, especially in Western Europe, it hasn't really been rising very much. It's sort of leveled off. It could be that it will level off in the U.S., too. But clearly, there's enough of it going around here that it's absolutely critical to get resistance testing in everybody who's been diagnosed with HIV.
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This article was provided by TheBody.com. It is a part of the publication This Month in HIV.
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