What factors are responsible for the wide variation in CD4 cell response to HIV therapy? We already know that low levels of vitamin D at initiation of highly active antiretroviral therapy (HAART) are linked to increased progression of HIV. Recently, a group of researchers -- including Alison Abraham, Ph.D., a statistician and faculty member in the epidemiology department at Johns Hopkins Bloomberg School of Public Health -- looked at vitamin D levels at HAART initiation and their potential role in CD4 recovery in a large cohort of people living with HIV. The study authors controlled for age, race and CD4 nadir before starting HAART and adjusted for seasonal variation in vitamin D levels. I spoke with Abraham at AIDS 2016 in Durban, South Africa, where she presented the results of the study.
Thanks so much for speaking with me, Dr. Abraham. Please walk me through your study.
We were interested generally in vitamin D levels, both the active and the inactive form of vitamin D. We measured levels of vitamin D-25 and also 125 in the Multicenter AIDS Cohort Study [MACS], a cohort of HIV-infected and uninfected gay men. We wanted to see whether or not the prevalence of vitamin D deficiency was higher in men living with HIV, compared to not. This study, in particular, was looking at whether or not vitamin D levels at HAART initiation were associated with the plateau and the rate of rise of CD4 count after HAART initiation.
The study was not interventional; it was simply what subjects' vitamin D levels were currently. Perhaps [those with higher levels] were on supplements; perhaps they drink lots of milk; perhaps they get a lot of sun. Sun and diet are the two big sources for vitamin D; and then vitamin D-25 is converted to 125 for use by your cells.
Not surprisingly, we found that, first of all, there's a lot of heterogeneity in where people's CD4 levels go following HAART initiation. We know that CD4 count at initiation plays a big role. But among the strata of baseline CD4, people get to all sorts of levels.
Given that vitamin D can be immunoregulatory, we were really hoping we'd see that vitamin D levels, either 25 or more likely 125, were related to whether or not people attained higher CD4 plateaus or got there faster.
We used a bit of a fancy model. It's a nonlinear model that tries to really model that exponential rise in CD4. We looked at whether or not [vitamin D levels were] related to the final CD4 level or the plateau -- and also that curvature, how quickly it curves up to the plateau.
We found that vitamin D-25 levels were not really related to either of those two entities -- how fast you got to the top or where you finally got. Vitamin D-125 levels seemed to be just barely related to how fast you get there -- but clinically insignificant, in terms of the magnitude of that association. It's a very, very small bump in how fast you get to your final CD4 plateau.
Essentially, what this study is saying is that your vitamin D levels probably don't play a big role, but maybe a very minor role, in how fast you gain CD4 or where you get to following HAART initiation. Perhaps there is a chance in a follow-up study; there would be some particular population [for whom vitamin D levels would play a larger role]. But certainly, overall, it doesn't look like this is a panacea.
Considering that this was a non-interventional study, what are the implications or next steps in terms of potential interventions?
Of course, a next step would potentially be an interventional study. There have been lots of them. Most of those results are null. However, there hasn't really been a lot of work on the 125, active vitamin D, side of things. That would potentially be an avenue for looking at improvement of immune function -- the bump after HAART initiation. We have very minor evidence that you might get some small gains that way, using active vitamin D supplementation.
There are clinical downsides to active vitamin D supplementation. There would need to be a cost-benefit analysis. For very small gains, it might not be worth it. There are only a few populations they give active vitamin D to. They tend to be individuals with kidney dysfunction whose kidney function is so low that they can't convert 25 to 125 very easily.
Is there anything else you'd like to add?
Just the idea that there is a lot of room for investigating what may improve the final immune function that you gain after HAART initiation. Because we see so much heterogeneity -- and that wasn't the point of the study, but because we see so much -- it makes me think that there may be other things that we can look at to see if we can, in general, improve the results of HAART initiation. Why is it that some people get to practically normal CD4 levels and others get to very suboptimal levels? There's room for a lot of research in this area.
Thank you so much for speaking with me.
This transcript has been edited for clarity.