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ICAAC 2007: Chicago, Illinois; September 17-20, 2007

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ICAAC 2007 Study Summaries: An Interview With Lisa Ross

September 17, 2007

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Welcome. This is Erika Nelson reporting for The Body PRO. I'm in Chicago at ICAAC 2007, one of the year's major HIV conferences. Right now, I'm in the poster session where researchers are standing in front of their posters, discussing their research and answering questions. We'll hear directly from investigators in the forefront of HIV treatment, care and prevention. In this podcast, the researchers will introduce themselves and then summarize their study. I'll then ask a few questions.

I'm Lisa Ross, and I'm a researcher. I'm in the virology department at GlaxoSmithKline. This is a study called ALERT, and these are antiretroviral-naive patients who were treated with tenofovir [brand name: Viread; also known as TDF] QD (once daily) plus either fosamprenavir [brand name: Lexiva, Telzir; also known as FPV, 908] with 100 mg of ritonavir [brand name: Norvir; also known as RTV] QD, or atazanavir [brand name: Reyataz; also known as ATV] with 100 mg of ritonavir QD. There were 53 patients who were randomized into each of the two study arms, and the results in this poster represent the virologic failure results through week 48, which was the conclusion of the study.

Of these 106 patients, seven patients met the criteria for virologic failure in the study. Four of those patients were randomized to the fosamprenavir arm, and three of those patients were randomized to the atazanavir arm. What more did you want to know?

I'd like to know what you found the ultimate significance of this to be.

I think the ultimate significance was that we were very pleased that we had a very low level of virologic failure on either arm. The numbers were very similar in terms of the virologic failures. One of the things that was interesting is that some of the patients who were on the fosamprenavir arm, because of the way the study was done, these patients were genotyped after they met the criteria for virologic failure.

So we did the genotyping of both the baseline time point and the virologic failure time point, and in some cases, some of the intermediate time points, what we found is that some of the patients on the fosamprenavir arm had evidence of transmitted drug resistance at baseline.

So, for example, patient 1 here in the study came into the study with thymidine analog mutations, and also came into the study with primary PI [protease inhibitor] mutations, and at baseline had reduced susceptibility using the Monogram PhenoSense assay to four different protease inhibitors. So this was a patient who already had mutations and reduced susceptibility that compromised the study drug regimen. So it was probably less surprising that they failed, because they had reduced susceptibility at baseline.

Patient number 3 on the fosamprenavir arm also came into the study with reduced susceptibility to fosamprenavir at baseline. Patient number 2 was very interesting. This patient, by population genotype, is wild type at baseline, as you can see on this graph, but at failure, which occurred at week 48, the patient had an MI84V, M184V, L210W, T215SY mixture in their virus.

As you know, when you fail on a tenofovir-based regimen, the primary resistance mutations you tend to see are K65R. So, considering that this patient had these thymidine analog mutations, it's very suggestive that this patient probably had archived resistance, archived transmitted resistance, that was not picked up by population genotyping, but emerged because this would impact the tenofovir/FTC [generic name: emtricitabine; brand name: Emtriva] portion of the regimen, making it incomplete virologic suppression because of the presence of those mutations, which ultimately could have been the reason that they failed.

Then, the other thing is that we are in the process of doing clonal analysis on the baseline and failure samples for all these patients, because we would like to understand it better. Also, some of the patients who failed in the atazanavir arm failed without detectable major protease resistance mutations, but they did have phenotypic reduced susceptibility to atazanavir, or other protease inhibitors, which suggests that maybe there was some low-level protease resistance mutations that were present at failure -- not at baseline, in this case, but at failure -- that we just couldn't detect by population genotyping.

Any limitations of this study?

It's a 106-patient study. A smaller cohort is not as good as a larger cohort. It was not powered, I don't believe, because it was a smaller sized cohort, to be able to make conclusions about inferiority or superiority. What we can say, again, is that we have seven failures: four in one arm, three on the other arm.

Dr. Ross, thank you very much.

You're welcome.

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