February 6, 2008
There's nothing like hearing the results of studies directly from those who actually conducted the research. It is these women and men who are transforming HIV treatment and care. In this interview, you'll meet one of these impressive HIV researchers and read an explanation of the study she is presenting at CROI 2008. Accompanying me on this interview is Dr. Gerald Pierone, an HIV clinician/researcher and the founder and executive director of the AIDS Research and Treatment Center of the Treasure Coast in Fort Pierce, Florida.
Barbara da Silva, M.D.
: I'm Barbara da Silva, with Abbott [Laboratories], Medical Director. This study was designed as a Kaletra [lopinavir/ritonavir, LPV/r] simplification study, comparing Kaletra simplification versus efavirenz [EFV, Sustiva, Stocrin] combination therapy in antiretroviral-naive patients.1 This sub-analysis was done to look at the DEXA [dual energy X-ray absorptiometry] scans within the study, looking at total bone mineral density.
We had a total of almost 100 subjects that had bone mineral density or DEXA scans within the study. What was found, when we looked at baseline, was that lower body weight and Caucasian race were both associated with lower bone mineral density. Something that was a little counterintuitive was that lower baseline HIV-RNA level was associated with lower bone mineral density.
When we looked, then, through two years -- which was the follow-up time of the study, 96 weeks -- we saw about 2.5% bone loss in both treatment groups. No difference between Kaletra or efavirenz, and no change when the nukes [nucleoside/tide reverse transcriptase inhibitors] were discontinued. When we looked at subjects that had the greatest bone loss -- defined as being clinically significant, as 5% [decrease in bone mineral density] -- we found that a low baseline CD4 cell count was predictive of greater bone loss. As well, Caucasian race was predictive of greater bone loss. [These were] the two big factors.
The main take-home from this study was that we didn't see differences between the classes: PI [protease inhibitor] -- Kaletra, in this case -- and efavirenz. But we were seeing bone loss upon ART [antiretroviral therapy] initiation. It didn't change when you discontinued the nukes within the study.
Bonnie Goldman: What was the gender ratio?
Barbara da Silva: It's exactly 78% [male] in both arms, [about] 20% female.
Bonnie Goldman: And racially?
Barbara da Silva: Sixty-six percent were Caucasian, 26% to 30% were black.
Gerald Pierone: Hi, this is Gerry Pierone from the AIDS Research and Treatment Center of the Treasure Coast. Were there any results in this study that were contrary to what you expected?
Barbara da Silva: Yes, the one result [that surprised me] was the baseline association of lower HIV-RNA levels with lower bone mineral density. You would have expected, probably, higher viral loads to be associated with lower bone mineral density, but that's not what we saw. We did adjust, because we thought maybe it was that the non-Caucasian race may have been coming into the study with higher viral loads, and that might have been why we were seeing the association that we did. But even with that adjustment, it still fell out as being a positive factor. It's unexplained, but it's something the study showed.
The other thing was that the greatest decreases in bone mineral density were associated with fasting glucose. When we looked at other metabolic parameters that included measures within oral glucose tolerance tests, they did not come out as being predictive. We think that result probably was a red herring, probably not a true result in the study.
Gerald Pierone: It seems like there are not a lot of data on the evolution of bone mineral density in treatment naive patients who undergo antiretroviral therapy. The one other study that comes to mind is Gilead .2 It looks somewhat similar to the data that you're presenting today.
Barbara da Silva: Yes. I think our data, if you followed it out, may show a similar tendency. But I think other studies have shown that too, that there may be a decrease with ART initiation and then a plateauing. We can't speak to it because our data just go through two years of follow-up, but certainly the data don't go against it either.
Bonnie Goldman: What are some of the limitations of the study?
Barbara da Silva: The big limitation between the way we've done the study and [the way] other groups have done the study is that the DEXA [scans] were not done specifically to assess bone mineral density. They were actually performed to assess body fat changes, so they're not lumbar, spine, or hip specific.
Bonnie Goldman: Thank you very much.
This transcript has been lightly edited for clarity.