More Options for Treatment-Experienced HIV-Positive Patients

Paul E. Sax, MD


March 14, 2013

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Hello. This is Dr. Paul Sax from Brigham and Women's Hospital and Harvard Medical School. I'd like to continue our discussion of interesting papers and presentations from the 20th Conference on Retroviruses and Opportunistic Infections (CROI), which just completed in Atlanta.

I'd like to summarize 3 very important studies in treatment-experienced patients. The first of these is the OPTIONS study.[1] The OPTIONS study asks the question: If you have more than 2 other active drugs in your salvage regimen, as estimated by phenotype and genotype testing, is it necessary to continue nucleoside analogues?

The study was very ambitious. It was a randomized-strategy study. All patients enrolled had to have a phenotypic susceptibility score of more than 2 aside from the nucleoside, and then they were randomly assigned to either a nucleoside-free regimen or a nucleoside-containing regimen.

The bottom line is that virologic outcomes were the same for both treatment arms. The nucleoside addition did not appear to add greater efficacy. Another finding -- which was unexpected -- was that there were 6 deaths in the nucleoside arm and none in the nucleoside-sparing arm; the total sample size was about 350. This is a difference in deaths that really can't be explained by the nucleosides because the death did not appear to be drug related; maybe it just occurred by chance.

The second study of considerable interest is the so-called SECOND-LINE study.[2] (This is one of several posters that in most conferences would definitely be a presentation.) It looked at patients who failed a first-line regimen of 2 nucleoside analogues and an NNRTI and who were then randomly assigned to receive either a nucleoside-plus-boosted-lopinavir regimen or a raltegravir-plus-boosted-lopinavir regimen.

Here, again, the study outcomes were about the same. Both study arms did quite well. Not surprisingly, virologic suppression was faster in the raltegravir arm, but I suspect that adherence here was critical. Of the patients who took their medicines, virtually all of them would have been virologically suppressed because they had fully active boosted protease inhibitors and at least partially active nucleosides. If you think about it, it's a bit surprising that the boosted-lopinavir-plus-raltegravir arm didn't do better, because there, patients were getting 2 fully active drugs after failure of the first regimen. I strongly suspect that it was adherence that drove the results.

The third study is called SAILING, which is another dolutegravir study.[3] (All of the dolutegravir studies, you'll note, have "ING" in them for whatever reason.)

SAILING looked at patients who were integrase-inhibitor naive and failing their current regimen, and who were randomly assigned to receive either a dolutegravir-based salvage regimen once a day or a raltegravir-based salvage regimen twice a day (raltegravir is given twice a day, dolutegravir once a day). Obviously, study participants would also have an optimized background regimen.

At 24 weeks in a planned interim analysis, the dolutegravir arm was statistically superior to the raltegravir arm. If you look at baseline characteristics, a lot of this difference was driven by the more difficult-to-treat patients, the patients with the higher viral loads, and the patients who didn't necessarily have active darunavir in their regimen, suggesting that this was a real difference -- maybe from the better pharmacokinetics of dolutegravir, maybe the potency; we'll have to see. This is not the final study result, but still, it is notable that at interim results at week 24, dolutegravir was superior.

Those are 3 very interesting studies and of practical importance for our patients: the OPTIONS study suggesting that you do not need NRTIs if you have more than 2 other active agents; the SECOND-LINE study showing that boosted lopinavir plus either nucleosides or raltegravir is a good second-line option after failing an NNRTI-based regimen; and another promising study for dolutegravir, the SAILING study.

That completes my discussion of these papers for today. I'll be speaking to you about some additional studies from CROI very soon. Thank you.