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.
The 934 study was a study of treatment-naive patients that enrolled about 500 patients, originally randomized to take tenofovir [TDF, Viread], FTC [emtricitabine, Emtriva] and efavirenz [EFV, Sustiva, Stocrin], versus AZT/3TC [zidovudine/lamivudine, Combivir] and efavirenz.
The study ended after three years, showing that the tenofovir/FTC/efavirenz arm had similar efficacy and better metabolic parameters than the AZT/3TC/efavirenz arm.
In this rollover study, all those patients were switched to a triple-combination, single-tablet regimen of efavirenz, FTC and tenofovir -- what is commercially known as Atripla. So you have now 517 patients switching to Atripla from two different regimens.
Essentially, during the first 48 weeks after the patients switched from those regimens to Atripla, there was no significant virologic failure. We paid attention specifically to the patients that were originally taking Combivir and efavirenz, because they were switching to a new regimen. But they remained virologically suppressed.
We also paid attention to creatinine clearance. There were no changes in creatinine clearance.
We also watched those patients that switched from Combivir/efavirenz to the triple combination of efavirenz, FTC and tenofovir for side effects, specifically regarding renal changes, given the fact that tenofovir has been associated with decreasing glomerular filtration rates. During those 48 weeks, we see that there were no clinically significant changes in the estimated glomerular filtration rate, when it was measured by either Cockcroft-Gault equation or MDRD [Modification of Diet in Renal Disease].
I think that the most significant finding of this study was what happened with the total limb fat that was measured by DEXA [dual energy X-ray absorptiometry] scan. It was very interesting that, at baseline, when those patients switched from Combivir to a tenofovir-containing regimen, they did not continue to lose fat. Originally, the loss in fat three years earlier was about 7 to 8 kilograms. In the first three years of the 934 study, it decreased to 5.5. In the prospective year, in which they were switched from Combivir to tenofovir, they did not lose any more fat. In fact, they gained .2 grams of fat. It's probably not clinically significant, but I think that what was clinically significant is that they did not continue to lose fat.
So it isn't clear if, after a patient has been on Combivir for three years, switching to tenofovir will revert the lipoatrophy and the fat loss, but at least we know that it apparently doesn't continue to get worse. This was one of the most interesting findings in this particular study.
Was there anything surprising about the findings?
I was expecting more improvement in the DEXA scan. The fact that in one year it only went from a median of 5.5 to a median of 5.7, for me was a little disappointing. There is a similar study using d4T [stavudine, Zerit], in which, one year after the patient was taken off of d4T, the fat gain has been significantly higher. So I was a little disappointed that the fat gain in this study was only .2.
Is this study going to continue?
No. The study has ended. So we will not know if the continued use of tenofovir by those patients that came off Combivir will further increase fat content. That will remain unknown.
This transcript has been lightly edited for clarity.