October 26, 2008
There's nothing like hearing the results of studies directly from those who actually conducted the research. In this interview, you'll meet one of these impressive HIV researchers and read his explanation of the study he presented at ICAAC/IDSA 2008.
My name is Tony Mills. I'm presenting information on the 96-week data from the ARTEMIS trial, which was a treatment-naive trial looking at patients who were randomized to either receive boosted darunavir [TMC114, Prezista] or boosted lopinavir [lopinavir/ritonavir, LPV/r, Kaletra], both in combination with tenofovir [TDF, Viread] and FTC [emtricitabine, Emtriva].1 This was the 96-week data. We have seen the 24- and 48-week data previously.2
Tony Mills, M.D.
What this data showed was, at 96 weeks, there did appear to be a statistically significant separation between the darunavir arm and the lopinavir arm, with darunavir outperforming lopinavir at 96 weeks on the TLOVR [time to loss of virologic response] analysis.
The change there was probably driven by a couple of things. There's some adverse-event difference between the two groups: There were more adverse events in the lopinavir group. But there were also virologic differences that we saw, and that played out in the patients who had a greater than 100,000 viral load, and patients who also had a lower CD4 count. There just appeared to be a virologic benefit to the darunavir over the lopinavir.
Could you talk about the percentages?
We had 79% of the people undetectable, meaning less than 50 copies in the TLOVR analysis, on the darunavir arm, versus 71% in the lopinavir arm.
What were some of the side effects?
Both medications are pretty well tolerated. We saw more gastrointestinal side effects in the lopinavir arm. We saw a little bit of hyperlipidemia in both arms. It was pretty evenly distributed between the two groups. We looked at lipids themselves: The HDL [high-density lipoprotein] and LDL [low-density lipoprotein] were pretty comparable between the lopinavir and the darunavir arms. The triglycerides were higher in the lopinavir arm -- again, as we would have expected.
Was there any difference from the 48-week analysis?
Yes. We showed non-inferiority at 48 weeks, but what we saw at the 96-week endpoint was that there was statistical significance as far as superiority.
Do you think the side effects contributed to this?
I do think side effects contributed. I think that not all side effects present themselves in the first 48 weeks of treatment, and sometimes patients have ongoing side effects that they're [initially] willing to tolerate. Then, as time goes by, they become less and less tolerant of those things.
Overall, the thing I was most impressed about as an investigator was that the boosted darunavir is an amazingly well-tolerated regimen. A lot of the patients that I put on the trial were newly diagnosed; they had no experience with HIV in the past. What they kept asking me was, "Why are you asking me about side effects? Why do I have to come back every two months?" Because they just tolerated the medication regimen so incredibly well.
Darunavir was just approved by the U.S. Food and Drug Administration for first-line use. Do you think it's going to be long before we see it in the U.S. treatment guidelines?
I think we will see it in the guidelines very soon. It's already in the IAS [International AIDS Society] guidelines, and I think it's just a matter of time before it gets in all the guidelines.
It's a great new agent to have in our armamentarium. We have a lot of great new agents, so it will be exciting to see over the next couple of years how the treatment paradigm changes, whether PIs [protease inhibitors] are going to continue to be our first-line agents [of choice or] other agents will be first line. But what this definitely gives us is a good, very effective, very well-tolerated, potent and durable PI to use as first-line therapy.
This transcript has been lightly edited for clarity.