March 30, 2011
The following is our transcript of a press conference that took place on March 1 at CROI 2011. In it, Peter Havens, M.D., summarized the findings of a study he was presenting at the conference entitled, "Vitamin D3 Supplementation Decreases PTH in HIV-infected Youth Being Treated With TDF-Containing Combination ART: A Randomized, Double-blind, Placebo-controlled Multicenter Trial: Adolescent Trials Network Study 063." The study's chief findings are that increases in parathyroid hormone (PTH) appear to occur in young adults taking tenofovir (TDF, Viread) regardless of vitamin D deficiency, but that vitamin D supplementation may nonetheless decrease PTH levels in these individuals.
Peter Havens: I'm here representing the Adolescent Trials Network, which is halfway between the IMPAACT [International Maternal Pediatric Adolescent AIDS Clinical Trials Group], which is for children, and the Adult ACTG [AIDS Clinical Trials Group]. This is a group that does multi-center trials on adolescents and young adults with HIV.
We've heard that HIV and its therapy are bad for bones. Tenofovir (TDF, Viread), a very potent and commonly used antiretroviral, has a history of maybe being worse for bones than other antiretrovirals. So it's on that background that we did this study.
Vitamin D deficiency: also bad for bones. The hallmark of vitamin D deficiency is an elevation in parathyroid hormone [PTH]. When your parathyroid hormone goes up, it says, "My body's not happy about something related to calcium."
Tenofovir, since its early use, has been associated with high parathyroid hormone. So you have high parathyroid hormone with vitamin D deficiency, and high parathyroid hormone in people taking tenofovir.
So we asked ourselves: Would treatment with vitamin D, which improves -- brings down -- the parathyroid hormone in vitamin D deficient patients; would that bring down the parathyroid hormone in patients taking tenofovir -- since, in some ways, tenofovir use looks like vitamin D deficiency from the perspective of having an elevation in parathyroid hormone?
The first thing we did was look at youth; mean age of 21. And it's important to recognize the Adolescent Trials Network; there were 37% women in this trial, and half were African-American. So this is a very special population, which actually looks a lot like the population of young people in the United States getting treated with tenofovir. We enrolled them based on: Are you taking tenofovir or not taking tenofovir? And then randomized within tenofovir and no tenofovir.
So we were able to, at baseline, show you, first of all, that tenofovir, yes -- more than other antiretrovirals, and controlling for all those other things about HIV infection -- is associated with a high PTH. And, importantly, the high PTH associated with tenofovir was found equally in people with vitamin D deficiency or no vitamin D deficiency.
So if you're on tenofovir, even if you've got a normal amount of vitamin D, your parathyroid hormone will be high, suggesting your body is not happy somewhere about calcium, and that may be bad for bones.
Then, for all those people we randomized to either vitamin D or placebo in an adolescent-friendly dose -- the dosing was 50,000 units of vitamin D3 once a month -- so that we could directly observe the therapy, and people didn't have to burden themselves by taking a pill every day, a huge problem for young adults. So with that, vitamin D once a month, a short study -- three months -- we showed that in patients taking tenofovir, their parathyroid hormone came down. Not to the low levels that we would see in people who were not on tenofovir. But we were able to decrease the parathyroid hormone in patients taking tenofovir. In patients not taking tenofovir, the vitamin D had no effect.
So if you're not on tenofovir and your parathyroid hormone is normal, your bones seem relatively happy; if you're on tenofovir, your parathyroid hormone is high, your bones seem maybe not so happy. And when you give vitamin D, we can bring down the parathyroid hormone somewhat. Thank you.
Reporter #1: Dr. Havens, the endpoint of your study was change in parathyroid?
Peter Havens: Yes, sir.
Michael Smith: There was no endpoint, in terms of clinical -- parathyroid is a marker. It's not a clinical result.
Peter Havens: Exactly right. Call it a pilot study, then.
Judith Currier: Can I just add something? I think one thing clinicians have wondered is whether standard vitamin D replacement strategies would be effective in people with HIV. And I think the study showed that this regimen was, for those who had low levels, very effective, right? Can you comment on that, in terms of raising the vitamin D level?
Peter Havens: There are a couple issues. You use the word "standard," which made me cringe. The Institute of Medicine [IOM] recommends 600 units of vitamin D. This was 50,000 units, every 30 days. So it's about 1,700 units of vitamin D a day, essentially, but given as a single dose. So it's higher than the IOM-recommended vitamin D. But clearly we were able to correct vitamin D deficiency in 95% of the participants, 55% of whom were vitamin D deficient at baseline.
So the first question is: Can you correct vitamin D deficiency? Yes. The answer is yes. Your specific question was: Who cares? The answer is we brought down the PTH, which is the first step in trying to do a longer study looking at bone mineral density.
This was a short study with a preliminary endpoint, which was very reassuring. So then the long study of, vitamin D: yes/no; calcium: yes/no; and what's the appropriate vitamin D dose? I think that's where we're going right now.
No comments have been made.
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