October 27, 2008
Eric Daar, M.D., is Chief of the Division of HIV Medicine at Harbor-UCLA Medical Center and Professor of Medicine at the David Geffen School of Medicine at the University of California-Los Angeles.
I'd like to provide an overview of the key topics related to therapy that were presented at ICAAC/IDSA 2008 in Washington, D.C. This is one of the big infectious diseases meetings of the year, which attracts over 10,000 people from around the world to talk about a variety of different issues surrounding, or related to, infectious diseases, including a heavy focus on HIV and AIDS.
We continue to believe that there is increasing evidence that starting therapy earlier is better. The main downside of doing so is that therapies in the past have had side effects, have been difficult to take and weren't always successful. In the current era, we have much better treatment options that are easier to take, and the overall response rate -- the likelihood of people achieving our goal of undetectable levels of virus -- is higher than ever. At this conference, we saw some follow-up of several studies looking at options.
Traditionally, our therapies have included using so-called "nukes" [nucleoside reverse transcriptase inhibitors, or NRTIs] with either a Norvir (ritonavir)-boosted protease inhibitor (PI) or an NNRTI [non-nucleoside reverse transcriptase inhibitor] -- with Sustiva (efavirenz, Stocrin) being the most important NNRTI that we use in the clinic. This second option comes as a coformulated drug, Atripla (efavirenz/tenofovir/FTC): People are actually able to take two nukes and the NNRTI as a single pill once a day.
Not all people are good candidates for that therapy or can tolerate its side effects, and that's why it's so important that we have other options. Some of those include using these so-called "boosted" [with Norvir] protease inhibitors. At this meeting, we saw some extended follow-up, out to almost three years, of a study examining people who were receiving Lexiva (fosamprenavir, Telzir), a PI, along with Norvir and nucleosides that had been previously shown to be very well tolerated and as effective as current standard PIs.
In addition to the extended follow-up, there were studies at this conference showing that Lexiva can be used with less Norvir than we had previously used it with. People can actually take this combination now as a once-a-day regimen, with only one pill of Norvir to boost it. That's good news.
At this meeting, we actually learned that people who originally started on a standard dosing of Norvir can often reduce the dose. Obviously, you'd need to talk to your provider and make sure that you're a good candidate for something like this. But it does provide options, either for first-line treatment, or for simplification of current therapy.
Another study showed two years of follow-up with another boosted PI called Reyataz (atazanavir). This is a medication where the PI is one pill, the Norvir booster is one pill, and they're taken with nucleosides. Researchers compared this combination to one of the standard PI regimens, and demonstrated that, after a year, it was as effective as standard regimens in suppressing HIV at very high levels. It was also somewhat better tolerated than standard PI regimens, causing fewer changes in cholesterol and triglycerides, as well as less diarrhea. We saw, at this meeting, two years of follow-up, where this Reyataz-based combination continues to be well tolerated, and very, very effective.
Another follow-up study looked at yet another protease inhibitor, and this is particularly timely. It's a protease inhibitor called Prezista (darunavir, TMC114). It's taken with Norvir. In this study, people who were starting therapy for the first time received the Prezista and Norvir combination once a day, which was a new way of giving this drug. (We previously used it in people who had drug-resistant virus twice a day. In fact, the U.S. Food and Drug Administration just approved last week this particular indication, where you can use Prezista once a day in people starting therapy for the first time.)
We had previously seen a year of data on this regimen of Prezista, Norvir and NRTIs. It showed that, compared to a standard PI regimen, it was very, very effective. In addition, it was somewhat better tolerated, not only with regards to side effects like diarrhea, but also for the lipids. At two years, in a study presented here, all of this continued to be true.
Finally, the highlight of this meeting was a study that demonstrated that we can now move beyond our standard regimens of nukes and NNRTIs, or nukes and PIs, to nukes with a completely different class: integrase inhibitors. As you are probably aware, the first integrase inhibitor was approved within the past year; it's called Isentress (raltegravir, MK-0518). It's given as one pill, twice a day, along with other medications, in people who are HIV drug resistant. Researchers designed a very large trial and compared the standard of care -- nukes with the NNRTI Sustiva -- to nukes with the new integrase inhibitor, Isentress, given as one pill, twice a day.
What they demonstrated in this study was that the Isentress regimen was highly efficacious. In fact, it appeared to do just as well as the standard-of-care regimen at suppressing HIV in the overwhelming majority of people. In addition, Isentress appears to not be associated with substantial side effects -- in fact, there was less in the way of neurologic symptoms in the people who received it, versus the comparator arm.
So, now we have yet another option for people starting therapy for the first time. It appears to be relatively simple to take, well tolerated and very, very effective.
Ultimately, while any given individual only needs one drug, the more options we have available, the better: We can simplify or we can use therapy in an individual way, focusing on what the specific needs are for a given person. The key is to really talk to your health care provider about all of these options and make sure that you know what is right for you.
Thank you very much.
This transcript has been lightly edited for clarity.