BMS-986001 Bone, Metabolic Data Compare Well to Tenofovir Through 48 Weeks
October 10, 2014
This fascinates me -- that we're still asking questions like this.
Yeah, but you know why? We don't know the BMI. We don't know anything about these patients before their HIV. So unless we have a cohort like the MACS, where people are followed before HIV and then after HIV [infection], and then after drugs [to treat HIV], we're not going to be able to answer that.
The data we have from other studies is showing that visceral fat seems to correlate with inflammation markers. So we're saying that, "Oh, that's bad, because that's probably a little bit too much. It's not just a return to health; it's pathological." But I don't think we know that yet. The other thing people were worried about is lipoatrophy. So even though overall people gained fat, was there a subset of people who lost fat and had lipoatrophy?
And the answer is no, not really. Because when we look at the very stringent [definition of] subclinical lipoatrophy, which is a loss of 20% from baseline, you see that the tenofovir arm had even more people who had those losses versus the BMS-986001 arm. So it's even looking better than tenofovir from that point of view. And we know that you rarely see [lipoatrophy] on tenofovir. So it looks good.
And then, lastly, because it's a thymidine analogue, mitochondria are a big thing. People were worried that you're going to see mitochondrial DNA depletion. So we did fat biopsies, looking at mitochondrial DNA numbers. And the bottom line is, in all the arms, the changes in mitochondrial DNA were within the limit of the tests, the variability of the tests. There were no significant changes in either of the arms.
So it's good. It seems benign from the mitochondrial point of view.
How about lipid values?
The lipids: We don't have P values for those. But we looked at the usual: total LDL, HDL and triglycerides. And, at least visually, numerically it looks like there may be some differences with tenofovir -- tenofovir leading to less changes. But if you look at the absolute differences, we're talking about 5 mg, 7 mg of cholesterol. So it's really not that much.
Is it enough to be a concern for patients who may be within the danger zone of very high cholesterol?
This is too [early], after one year. This is really minimal absolute differences between the two [drugs].
Thymidine analogues have been around for a long time. How is it that we're now seeing -- within a span of a couple of years -- two really significant thymidines suddenly come through the pipeline?
Oncolys, the company [now developing the drug], had it at least for three or four years. But they were doing Phase 1 studies to make sure mitochondria looks really clean. I think that's what delayed it.
It was just extra cautiousness?
I think so, because it's a thymidine. I mean, they want to be very careful because nobody wants to put money in to discover that you're going to see the same problems that d4T had.
Now that we've got the rise of integrase inhibitors, what is the place for a new-generation thymidine analogue?
For most regimens, we still need NRTIs. I think people are trying to shy away from tenofovir now: They worry a little bit about abacavir and cardiovascular. They want the perfect NRTI that's benign, that doesn't have the kidney and renal [toxicity], so they can add it to dolutegravir [Tivicay, DTG] or other drugs. For the next 5 to 10 years we are still going to see most people use NRTIs, in addition to integrase, probably, as first-line.
I think for patients it's good to have a lot of options. I mean, you can't have just TAF as one NRTI.
Myles Helfand is the editorial director of TheBody.com and TheBodyPRO.com.
Follow Myles on Twitter: @MylesatTheBody.
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This article was provided by TheBodyPRO. It is a part of the publication The 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2014).
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