This Month in HIV: Breaking HIV/AIDS Research From CROI 2007
People came away from CROI 2007 with a different take home depending, I think, on their perspective and who they were. We thought it would be helpful to get the viewpoint of someone with HIV. Nelson attended CROI and came back with a unique take on the research presented.
So, Nelson, tell me: As a long-term survivor and community activist, do you think we have come closer to knowing when it is optimal to start HIV therapy? If you were newly diagnosed, when would you begin treatment?
I think we're getting closer. But we still have guidelines that tell physicians to prescribe to people that have a CD4 count under 350 or viral loads over 100,000 or a combination of the two or somebody that is actually showing symptoms of HIV or AIDS.
But I think we're getting closer and closer to the reality that we used to actually embrace a few years ago -- to start people at an earlier stage of HIV infection. We don't have anything when it comes to the U.S. HIV treatment guidelines that says that yet. I think we're going to move towards that. That's because, I think, the main factor here is the fact that we have a lot more friendly, or friendlier, treatments -- HIV treatments that are not as toxic and problematic as we used to have. For instance, five years ago, or six years ago, many of us were taking Crixivan [indinavir] plus Zerit [stavudine, d4T] and Videx [didanosine, ddI], and we had a lot of problems with neuropathy, lipodystrophy, lipoatrophy, kidney stones, insulin resistance, diabetes ... you name it. So we kind of walked away from the concept of treating people earlier on in the disease, not only because, even though we had good CD4 response and viral load responses back then, the toxicities were a little too much to justify early treatment.
"We have more and more data that shows there are, of course, immune benefits and viral load benefits to starting treatment earlier."
However, the past few years, we've had treatments come through the market that are a lot more friendly when it comes to toxicities. We have Viread and now, of course, Truvada [tenofovir/FTC], the once-a-day pill Atripla [efavirenz/tenofovir/FTC], Reyataz [atazanavir] a protease inhibitor that has definitely shown lower incidence of lipid abnormalities. We kind of got rid of Zerit. Zerit is not as popular in the United States as it used to be, although, of course, Zerit is being used everywhere else in the world. We cannot forget our brothers and sisters out in Africa and South America and Asia that are taking Zerit and AZT [Retrovir, zidovudine].
We have more and more data that shows there are, of course, immune benefits and viral load benefits to starting treatment earlier. The biggest factor in shifting the pendulum towards earlier treatment will eventually be less toxic treatments. We are already moving in that direction. I think the integrase inhibitor class is going to be shown, in my prediction, to be a lot cleaner in toxicities for treatment-naive patients, too. They are moving towards that. There's data from CROI on Tibotec's drug, TMC278. [Click here to read coverage of the study.] It's a non-nucleoside [reverse transcriptase inhibitor] like Sustiva [efavirenz, Stocrin] or Viramune [nevirapine] that may be as effective as Sustiva, yet not have the neurological complications.
The more drugs we have that are friendlier to patients' bodies, the more the pendulum will swing back to where we used to be, years ago. However, I'm also an activist, so the issue is, "Who's going to pay for earlier treatment?" We're already overburdened when it comes to getting funding from federal sources in the United States. The earlier we start people, the more money we have to spend on healthcare for HIV. That's a big factor, too, that we have to think about. It's not only about the health benefits. I think there's going to be some problems trying to -- especially under the current administration -- get programs funded that justify treatment, for instance, for somebody that has 450 T cells, instead of 350. That's what I'm trying to say.
There are many factors that determine when a person should start treatment. Some people may not choose to take treatment when they have high T cell levels and low viral loads. We have data now that show more and more that, for instance, the gut lymphatic tissue -- i.e., the T cells, the memory T cells in the lymphatic tissue in the gut -- are preserved better if we treat earlier, too.
Why is that important?
We forget that most of our immune system, most of our T cells, memory or naive T cells, are in the gut. In the past three years I myself, as a patient, I have experienced a lot of gut problems. I have had GI [gastrointestinal] problems since day one. I have lived with this for twenty-some years, and I'm always concerned about my gut. It seems like a huge loss of T cells, CD4 cells, memory cells, in the gut lymphatic tissue occurs early on in the disease. That [early loss of CD4 cells in the gut] basically predicts, or predisposes us, to a lower immune response with treatment in the future. So it seems like we lose a lot of memory T cells early on. If we treat it early on -- it's a hypothesis; I think we need to prove it; nobody has really proven it yet -- we may preserve immune function for the longer term.
You asked me a question which I don't think I've answered yet. If I just turned out to be positive today, let's say, and I had 400 T cells and maybe, let's say, 50,000-60,000 viral load, which would not qualify me for HIV treatment under the DHHS [U.S. Department of Health and Human Services] guidelines, would I take treatment? I probably would, as long as I could take a treatment that I can tolerate -- maybe a Truvada or Sustiva -- although I don't tolerate Sustiva very well. Or Truvada + Reyataz. Things of that nature that would not affect me metabolically, or my gut would not be affected. Diarrhea is a big issue for me. Yes, I would definitely consider it. I would be more open to that knowing the data that I've seen at CROI.
Would you consider starting treatment with a CD4 count of 450?
Yes, but I'm also a pill popper. Some people do not want to pop pills, and they have a big barrier to taking medication of any kind. So I think we have some more work to do. I think we're going to move towards that. I think it will probably take a few -- two or three -- years to get there. I really think so ... It's looking more and more promising with less toxic drugs.
My second question is related to my first. Should people who are lucky enough -- or unlucky enough -- to find out they have HIV immediately after getting infected (that's called primary infection) -- start treatment immediately? Did you see any interesting research on the topic at CROI?
It's kind of a gray area. And also, who's lucky enough to run to a doctor while they're going through basically primary infection? They just find out. They don't even find out, actually. They have unsafe sex, and they can feel their bodies changing. They're having night sweats. They're having flu-like symptoms. Their lymph nodes are inflamed. They run to the doctor. The doctor runs their viral load and T cells. Of course, their viral load, it really increases dramatically in that phase. And they get treatment.
Very few people do that. Very few people. [Laughs.] Most people are actually in denial in the first months, or actually, years, of infection, anyway. We are talking about people who actually are smart enough to do that, to run to the doctor and say, "Hey, I may have been infected. Test me. Let's run a viral load, and let's do something about it."
For those people, some studies have shown some benefits from early treatment. Of course, we have studies that show no benefits. But two studies that were presented at CROI were very interesting. One was done in Amsterdam with 332 patients. ... Sixty-four people enrolled in the study started HAART within 180 days of seroconversion, and 32 of these patients then stopped treatment. I forget how many months later, but it was a few months later. What they found out is that for those patients that started treatment right away, within 180 days of seroconversion -- I don't think that's really right away, by the way; it could have been, probably, earlier, to be more effective -- they found that their viral set point was a lot lower once they interrupted HAART. They went on a treatment interruption.
The viral set point for patients treated within 180 days of infection was lower compared to patients who began treatment more than 180 days after seroconversion?
Right. Compared to the arm that was not treated early. But they say that that benefit tended to disappear with time. Of course, viral loads started going up after that. But when they interrupted, compared to those that were not treated early, their viral load was almost .6 log lower.
That makes sense. If you treat early maybe you have some preservation of immune response, but with time, that effect may disappear.
There's another study from Munich, too, that enrolled 200 patients with primary HIV infection. One hundred forty-four were treated right away, and 56 patients delayed treatment. Then they stopped -- 100 patients stopped treatment after almost ten months. And in this study they didn't quite see the differences, the huge differences, in viral load, between treated and untreated that were seen in the study done in Amsterdam, but they saw 87 T cells more in patients who were treated early. The treated arm had a lot more T cells than those others that delayed treatment.
There's actually another study that I haven't mentioned that says that, once again, the gut lymphatic tissue, can be preserved. The CD4 loss that occurs early on in HIV infection can actually be improved if you give treatment early on. That's another area of research that I think we're going to see a lot more studies on.
It's very exciting. I don't think we have an agreement. I think actually this is probably the most controversial part of HIV treatment. I think there are trends that will show us that maybe it is not a bad idea to treat people -- especially now that, once again, we have less toxic drugs to treat them, at least for the first year of their infection. We can see what happens afterwards.
"Why is Sustiva causing a higher incidence of lipoatrophy in the presence of nucleosides? Is it because of the increase of intercellular levels of AZT or d4T? Or is it related to something, when it comes to mitochondrial toxicity of insulin resistance? It's very intriguing."
One more thing I wanted to add that was really shocking for me is that, in the Munich study, [of] those that started treatment and then stopped 12 months later there were two patients that remained undetectable, even after they stopped treatment. I'm hearing a lot more of that. When I go out on my lectures, people raise their hands and say, "Well, I was in treatment. My T cells went up, my viral load went undetectable. Then I wanted a break and had some issues with side effects and took a treatment interruption, and I'm still undetectable. What do you think about that? Am I cured?"
Back two years ago, I thought, "Hmm. Maybe you were diagnosed wrong, right?" [Laughs.] But now I'm seeing more and more of that. So there are some patients -- very few of them -- that start treatment early, go on a treatment interruption and remain undetectable. I'm not saying this is a rule, obviously. Only two out of 100 remained undetectable after months of stopping therapy. That means we need to look at these patients more closely, too. We should ask what's happening to them and why treating them early gave them this kind of response.
We have to jump to the next topic, because our time is limited. Can we talk about your specialty, metabolic complications? Did you see anything interesting on the topic at CROI?
Yes. The study [ACTG 5142] considering Sustiva plus nucleosides, versus Kaletra plus nucleosides, versus Kaletra plus Sustiva without nucleosides. Very interesting. They found a higher incidence of lipoatrophy in the Sustiva plus nucleoside arm versus Kaletra. Definitely something we did not expect at all. So, of course, the nucleosides included AZT, d4T, and I think some patients were also on tenofovir [Viread]. But what we saw is there's a higher incidence of lipoatrophy in the Sustiva arm than in those who are taking also AZT or d4T. I think somebody needs to explain this, and we're going to see data on this eventually, I guess: Why is Sustiva causing a higher incidence of lipoatrophy in the presence of nucleosides? Is it because of the increase of intercellular levels of AZT or d4T? Or is it related to something, when it comes to mitochondrial toxicity of insulin resistance? So it's very intriguing, very intriguing.
"DEXA is a beautiful thing. DEXA scans cost under $150, with them you can get information about your bone density, your lean body mass, your fat mass, in every single part of your body."
There's another study that ... looked at bone density and the treatment of people with low bone density with Fosamax [alendronate] once a week, and calcium and vitamin D supplements. There was a response to Fosamax. It was almost like a 3 percent or so increase -- yes, a 3.38 percent increase in 48 weeks. People say, "Well, that's not much," but the encouraging thing is that it's actually the same response that has been shown in HIV-negative studies in the past. At least we know that this treatment, Fosamax with supplements of calcium and vitamin D, works the same way for HIV-positives and negatives. That was very interesting, too.
I'm one of those activists trying to push for early diagnosis of bone density loss with the use of DEXA [dual energy X-ray absorptiometry] scans. There's also no recommendations, no guidelines, on this topic. I think the earlier we find out whether or not you have problems with bone density, the better. Most people wait until they have a fracture.
Have you gotten a DEXA scan?
Oh, yes, yes. DEXA is a beautiful thing. DEXA scans cost under $150. With them you can get information about your bone density, your lean body mass, your fat mass, in every single part of your body. Let's say we were in an extremely rich society where everybody had good health care. Having a baseline DEXA scan for all of us -- and probably you could get one every two years or so, three years, to see how our bodies are changing, not only because of HIV, but because of aging -- and treating accordingly would be ideal. In a perfect world, that's what we should be doing. DEXA gives you three pieces of information.
So if someone's insurance covers it, you would recommend DEXA?
Yes. I don't recommend anything; I'm a patient. I'm not a doctor. But, yes, yes. It should be a full body scan, though. There are three types of DEXA scans. You can do a spinal DEXA. No. Get a full body DEXA that tells you how much lean body mass, muscle, of course, and fat and bone density you have in every single part of your body. Put it in your chart and have your doctor recheck it two or three years later. Make sure you're doing OK. If not, treat.
Also, I tell people to exercise with weights. Make sure your testosterone is normal and your thyroid hormones are normal because low hormones can decrease bone density and exercise has been shown to increase bone density.
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This article was provided by TheBody. It is a part of the publication This Month in HIV.
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