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An Interview With Nancy Crum-Cianflone, M.D.

October 28, 2008

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I'm Dr. Nancy Crum-Cianflone. I'm from the Tri-Service AIDS Clinical Consortium with the Infectious Disease Clinical Research Program. We did a study to look at whether initial CD4 counts among HIV seroconverters have changed over the course of the epidemic.1

Nancy Crum-Cianflone, M.D.
Nancy Crum-Cianflone, M.D.
Thus far, there's been literature looking at this, but it's been conflicting. Some studies in the United States have suggested that CD4 counts might be changing and others have not found an association. However, many of these studies were small, did not include seroconverters or spanned short periods of time.

We conducted a study in our natural history study as part of the Tri-Service AIDS Clinical Consortium to look at the initial CD4 count among HIV seroconverters from 1985 to 2004. We have 20 years of the HIV epidemic to examine.

We also looked at demographics, seroconversion times and time to first CD4 count, and we adjusted for all those factors in our models to make sure that if those things had changed over the epidemic, it could not account for the CD4 count changes.

We studied almost 2,000 HIV seroconverters. At the time of their HIV diagnosis, the mean age was 30 years old. Most of our population is male because we work in a military consortium. About 50% were white versus 50% African Americans. The time from their last negative HIV test to their first positive test was a mean of 1.5 years; very close windows between negative and positive tests.

What we found is that the CD4 count appears to have significantly decreased over the course of the epidemic. In fact, at the beginning of the epidemic, from 1985 to 1990, the mean CD4 count was 632, whereas today it's 499, a drop of over 100 cells. We found the same finding despite adjusting our models for demographics and changes that might have occurred in the population over the course of the epidemic.

We also looked at the CD4 percentage, just to assure ourselves that it was not a laboratory testing change or other change that might have accounted for our findings. We also found the CD4 percentage had changed over time. However, other immune cells, such as the white count or the lymphocyte count, did not change over time, which would support the fact that this wasn't a change in how we're doing laboratory testing, but was a true finding.

In conclusion, it appears that there has been a significant decline in the CD4 count at initial presentation among our HIV patients. We did not see a change in other immune cells that would help to predict why this would be the case. I also want to point out that not only did the CD4 count seem to have fallen by a mean of 100 cells over the course of the epidemic, but this has now resulted in, in the latest time period, about a quarter of our population presenting with a CD4 count less than 350, which is the current guideline for the initiation of HAART. So whereas we used to think patients had a several-year window between diagnosis and actually needing to go on antiretrovirals, at least a quarter of our patients should start HAART immediately.

We don't really know why the CD4 counts are falling, and this study did not examine this. One hypothesis might be that HIV has evolved and is becoming more virulent and more able to destroy the CD4 counts early after infection.

Have there been any other studies to show that HIV is becoming more virulent?

There was a large study from a European cohort that showed similar decreases in the initial CD4 count over the course of the epidemic. This study was based only on a U.S. population and shows a similar phenomenon has happened in the United States.

In terms of actually showing that HIV is or isn't more virulent, that hasn't been done yet.

Do you think these findings might just be due to people accessing treatment later?

I don't think so, because this is a military cohort that has free, open access all the time to medical care. Each of our patients has an HIV-negative date and a positive date, so we can exactly determine, very narrowly, when they got their HIV. It's not a matter of people presenting later or having less access, because we have full access and we have mandatory CD4 counts being determined and HIV tests being determined in our population. So I don't think that can explain our findings or the European cohort's findings.

Could there be any lead-time bias?

I don't think there's lead-time bias. We have documented negative time and we've got documented positive time, and the time in between the two has stayed 1.5 years through the course of the epidemic. That window hasn't gotten longer or shorter as the epidemic has taken place. So I don't think that can explain the difference we're seeing [between] each period, because the converting windows are the same throughout all periods.

Let's say that HIV is becoming more virulent. It wouldn't have any clinical manifestations, right?

A patient probably won't feel sicker as this is happening. But the clinical significance, I think, is that this should encourage patients who might have contracted HIV to get tested and come into clinical care earlier. Because in truth, if their CD4 counts are falling faster, then they're going to reach an AIDS diagnosis or the need to initiate treatment according to HAART guideline indications sooner. So they may not have as long a time between their contraction of HIV and actually progressing in terms of disease state.

Thank you very much.

This transcript has been lightly edited for clarity.



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ICAAC/IDSA 2008 Newsroom
