The Body Covers: The 15th Conference on Retroviruses and Opportunistic Infections
CD4+ Cell Count Declines Slowly, But Steadily, in Elite HIV Controllers, Small Study Finds
An Interview With Hans-Jürgen Stellbrink, M.D.
February 6, 2008
There's nothing like hearing the results of studies directly from those who actually conducted the research. It is these women and men who are transforming HIV treatment and care. In this interview, you'll meet one of these impressive HIV researchers and read an explanation of the study he is presenting at CROI 2008. The interview was conducted by Gerald Pierone, M.D., an HIV clinician/researcher and the founder and executive director of the AIDS Research and Treatment Center of the Treasure Coast in Fort Pierce, Fla.
Hello, my name is Hans-Jürgen Stellbrink from the IPM [Immunologie Pathologie Molekularbiologie] Study Center [in] Hamburg, Germany.
We've made the observation that some people with optimal control of viremia in the absence of HAART [highly active antiretroviral therapy] -- that means less than 50 copies/mL all the time, without taking pills -- have experienced decreasing CD4+ cell counts over very long periods of follow-up. It might not be so apparent within short periods of time, but over long periods of time this seems to be a trend.
We were interested in seeing if this is true for more people than the individual cases we saw. Therefore we analyzed our cohort and calculated the slope of CD4+ cells.1 That means we drew a line through all the CD4+ cell [count readings] we have from our patients, and try to calculate if it goes down or up, or if it stays in the range of zero.
I would have expected people with no measurable viral load to have stable CD4+ cells. It's a small number of [elite controller] cases [examined in our study], it's only eight subjects, but [elite controller status is] very rare. It's only 1% of all HIV-infected people who have reached this stage. Actually, they seemed to uniformly have a negative development of CD4+ cells. It doesn't go down very much: It translates into a loss of approximately 50 cells per year. And these people could be different than other [elite controllers].
We tried to control [for discrepancies] by looking at their respective CD8+ cell counts to see if it was a technical problem of measurement because, over 16 years of follow-up, you change the techniques. But that doesn't seem to be the explanation. We also compared [these results] with people who have less well-controlled viremia, 50 to 5,000 copies; and with people who have therapeutically controlled viremia. As expected, [they all] have increasing CD4+ cells. That means that the slope goes up.
You mentioned that you looked at several different groups. Can you describe the different groups of patients that you studied?
The first group was the group of eight elite controllers, people who had no measurable viral load. They were only allowed to have one single measurement up to 200; sometimes [a measurement between 50 and 200 can be due to] technical reasons. [There was] a group of intermediate controllers, who had 50 to 5,000 copies; and [a group of] people on HAART. We were just interested in their long-term development of CD4+ cell counts.
You mentioned before that there can be variability in absolute CD4+ count because of different techniques. Did you also look at the CD4+ percentage?
We haven't formally analyzed that. That doesn't help us to see if there is a loss over time, because CD4+ percentage would also be influenced by CD8+ cell count. If [CD8+ cell count] increases, it could be that CD4+ percent goes down without decreasing absolute CD4+ cells. So we only did [our analysis] with absolute CD4+ cells.
It might be interesting to go back and look at that data as well.
Definitely. If you look at the stability of CD8+ cell counts over time, at least in this analysis, there should be a decrease in percentage.
What would you say the take-home message is for the clinician who has patients that appear to be elite or intermediate controllers -- who have very low viral load in the absence of HAART?
The take-home message would be to continue to follow them, to take into account that they might ultimately reach a point at which CD4+ cells [are low enough to] endanger them, where they might get infections. But it's going to take a very, very long time. They are relatively safe from complications, I think.
This [study] raises the issue of what we can currently achieve with vaccines. Because if you have a vaccine that achieves a non-progressive state or a controller's state, does that mean that the patient doesn't have to worry again for his whole life? And I think it probably doesn't [mean that]. I would expect this development [of a gradual CD4+ cell count reduction] to happen in these people too.
Are you planning further studies on this group of elite controllers? Immunologic or other exploratory trials?
Yes, we have done some trials, and some people here [at this conference] were interested in the question of whether we have data on replication. We did some lymph node studies and these [elite controllers], as far as we studied them -- just a subset of them -- have replication in the lymph node. It's not that they are aviremic due to no replication, but it's very, very limited within the lymph nodes. We are actually doing further immunological studies, trying to characterize them further on. This is just the initial step to see if our assumption was right.
OK, very good. Thank you.
This transcript has been lightly edited for clarity.
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