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Body Fat and Bone Changes After 96 Weeks of Fosamprenavir/Ritonavir
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48th ICAAC, October 25-28, 2008, Washington, DC
Mark Mascolini
People boosting fosamprenavir with 100 rather than 200 mg of ritonavir daily gained less arm fat through 96-weeks in a randomized trial, though changes in leg fat and trunk fat were similar with the two regimens [1]. Lumbar spine bone mineral density (BMD) fell more than 2% in 96 weeks with both regimens, which also contained abacavir/lamivudine. Sorting out reasons for arm-fat differences and other changes at week 96 is tough, however, because the trial was small to begin with and many of the 115 study participants did not make it to week 96.
COL100758 randomized previously untreated people to 100 or 200 mg of ritonavir once daily plus 1400 mg of fosamprenavir once daily and abacavir/lamivudine. (For antiretroviral-naive people, once-daily fosamprenavir is licensed for use with either 100 or 200 mg of ritonavir.) After 48 weeks the investigators saw no virologic response difference between the two groups [2] and no significant differences in fasting triglycerides, cholesterol, or limb or trunk fat [3].
Throughout the study the COL100758 investigators measured body fat and BMD with whole-body DEXA. They reckoned adherence with pill counts at each study visit. When the study began, median age stood at 39 years in 58 people randomized to 100 mg of ritonavir and at 40 years in 57 randomized to 200 mg. Four in 5 study participants were men, 63% in the 100-mg group and 55% in the 200-mg group were non-Caucasian, and about one quarter had a pretreatment viral load above 100,000 copies.
The 96-week analysis involved 40 people in the 100-mg ritonavir group and 31 in the 200-mg group. The investigators did not explain why 44 people (38% of those randomized) stopped follow-up before week 96 or whether those who continued had demographics and baseline values similar to the total original group.
After 96 weeks median arm fat fell 18 g in the 100-mg ritonavir group and rose 76 g in the 200-mg group. The difference in median percent change from baseline, -0.1% with 100 mg versus +11.6% for 200 mg, was not statistically significant. What these changes mean is hard to say because the arm-fat range was profound in both follow-up groups when the study began (293 to 10,751 g in the 100-mg group and 225 to 4421 g in the 200-mg group), as were the changes after 96 weeks (-2086 to +1024 g with 100 mg versus -1420 to +1832 g with 200 mg). Perhaps the most notable arm-fat finding is that percent change in arm fat stood on the plus side in both groups at 48 weeks (+7.0% and +6.6%) but at 96 weeks fell back to the minus side with 100 mg (-0.1%) while continuing to rise with 200 mg (+11.6%). (Week-48 follow-up involved 44 people taking 100 mg of ritonavir and 43 taking 200 mg.)
The investigators declined to speculate on why arm fat rose for 48 weeks in the group using the 100-mg boost, then fell through week 96. They suggested that "the effect of differential adherence to ritonavir between the two [trial] arms on changes in metabolic parameters is worth examination," but they noted that ritonavir adherence stood above 88% among all study participants. Both treatment groups had 100% adherence to fosamprenavir at 96 weeks and better than 90% adherence to abacavir/lamivudine. Adherence to 100 mg of ritonavir looked a little better at 96 weeks (94.5%) than did adherence to 200 mg (88.8%). As noted, 96-week follow-up also fell off more in the 200-mg group than in 100-mg group (69% taking 100 mg in follow-up at week 96, compared with 54% taking 200 mg).
BMD declines also seemed to progress at an uneven pace through 96 weeks of treatment with fosamprenavir/ritonavir. Here are median percent changes in total and lumbar spine BMD for people who continued follow-up in the two treatment arms for 48 and 96 weeks:
Number of people randomized: 115 (58 to 100 mg and 57 to 200 mg)
Total BMD
⋅ Week 48 (n = 87), 100 mg -0.60%, 200 mg -0.94%
⋅ Week 96 (n = 71), 100 mg -1.06%, 200 mg -1.04%
Lumbar spine BMD
⋅ Week 48 (n = 35), 100 mg -2.53%, 200 mg -0.80%
⋅ Week 96 (n = 27), 100 mg -2.99%, 200 mg -2.22%
If anything, these results suggest that a lot can happen to total and spine BMD between weeks 48 and 96 in people taking fosamprenavir with either dose of ritonavir--unless other variables for which the researchers could not account, or the dwindling sample sizes, explain these swings.
Median 96-week gains in leg fat were equivalent in the two groups (10.0% with 100 mg and 16.3% with 200 mg), as were median gains in trunk fat (14.5% with 100 mg and 18.5% with 200 mg). The different doses did not yield differing fasting lipid readings through 96 weeks.
The bottom line appears to be that 100 mg of ritonavir does as well virologically as 200 mg in boosting fosamprenavir in previously untreated people. And there seem to be no marked differences in this study between the two doses in metabolic abnormalities or body fat changes, except for a hard-to-explain arm-fat deficit with 100 mg.
References
1. Wohl DA, DeJesus E, Sloan L, et al. Fat changes by total body DEXA after 96 weeks of treatment with once-daily fosamprenavir with either 100 or 200 mg of ritonavir plus abacavir/lamivudine: COL10075. 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 25-28, 2008. Washington, DC. Abstract H-2302.
2. Hicks C, et al. Once-daily fosamprenavir boosted with either 100 mg or 200 mg of ritonavir along with abacavir/lamivudine: 48 week safety and efficacy results from COL100758. 11th European AIDS Conference. October 25-26, 2007. Madrid. Abstract P5.7/01.
3. Wohl DA, Lancaster T, DeJesus E, et al. Determination of body composition changes by total body dual-energy x-ray absorptiometry after 48 weeks of treatment with once-daily fosamprenavir boosted with two different doses of ritonavir plus abacavir/lamivudine: COL100758. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 22-25, 2007. Sydney. Abstract TUPEB080.
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