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Central Fat Accumulation in ART-naïve Subjects Randomized to ABC/3TC or TDF/FTC with ATV/r or EFV: ACTG A5224s, a Substudy of ACTG A5202
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Reported by Jules Levin
CROI 2011 March 2 Boston
Grace McComsey*1, D Kitch2, P Sax3, P Tebas4, C Tierney2, N Jahed2, L Myers5, K Melbourne6, B Ha7, and E Daar8
1Case Western Reserve Univ, Cleveland, OH, US; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Brigham and Women`s Hosp, Harvard Med Sch, Boston, MA, US; 4Univ of Pennsylvania, Philadelphia, US; 5Frontier Sci and Tech Res Fndn, Amherst, NY, US; 6Gilead Sci, Foster City, CA, US; 7GlaxoSmithKline, Research Triangle Park, NC, US; and 8Los Angeles Biomed Res Inst at Harbor-UCLA Med Ctr, Torrance, CA, US
AUTHOR CONCLUSIONS:
- Regmens containing TDF/FTC or ABC/3TC increased visceral abdominal fat & were not significantly different.
- ATV/r led to greater gains in trunk fat and a trend towards greater gains in visceral abdominal fat than EFV
- VAT:TAT did not change with any of the studied regimens likely due to the concomitant increase in both VAT & SAT
- On average individuals gained 1.8 kg of trunk fat; subjects on ATV/r gained 1.1 kg of trunk fat more than those on EFV
- Changes in CT & DEXA were consistent (VAT/SAT with trunk fat/limb fat, respectively)
In response to questioning from the audience Dr McComsey said at baseline patients had healthy BMIs (but if you look at baseline demograpics CD4 were low and 41% had >100,000 viral load.....We don't know if the increases in fat - VAT & SAT - are a return to health or if its unhealthy. Followup lab evaluations such as inflammation markers & other assays may help to understand these outcomes. Dr Capeau said I don't think an increase in VAT is a good thing.
"There was a trend towards higher VAT with ATV/r (mean change of 14%) larger than EFV at week 96 compared to EFV. The increase in VAT for all study arms was 19%. There was no difference in VAT change between ABC/3TC vs TDF/FTC.....The SAT difference between ATV/r & EFV at week 96 was 19%, ATV/r was associated with significantly more increase in SAT, while for the ABC & TDF comparison there was no difference. For all 4 study arms the overall increase in SAT was 24%"
Link to presentation:
http://app2.capitalreach.com/esp1204/servlet/tc?c=10164&cn=retro&s=20445&&dp=player.jsp&e=13724&mediaType=podiumVideo/
ABSTRACT
Background: The effects of abacavir/lamivudine (ABC/3TC) vs tenofovir DF/emtricitabine (TDF/FTC) combined with either efavirenz (EFV) or atazanavir/ritonavir (ATV/r) on central fat accumulation have not been compared.
Methods: A5224s was a metabolic substudy of the A5202 4-arm trial of HIV-infected, treatment-naïve subjects randomized equally to double-blinded ABC/3TC vs TDF/FTC with open-label EFV or ATV/r. A5224s endpoints included changes from baseline to week 96 in visceral adipose tissue (VAT) and VAT : total adipose tissue (TAT) ratio by CT scan. Post-hoc endpoints included trunk fat (by DEXA scan). Analyses were intent-to-treat with as-treated being secondary. Statistical tests included linear regression and 2 -sample t-test.
Results: We randomized 269 subjects (85% were male; 47% white non-Hispanics). At baseline, the median HIV-1 RNA was 4.6 log10 copies/mL, age 38 years, weight 76 kg, CD4 233 cells/mL, trunk fat 9.4 kg, VAT 84.1 cm2, and VAT:TAT 0.31. There was no significant evidence of an interaction between the NRTI and the EFV and ATV/r components for trunk fat, VAT, or VAT:TAT (all p ≥0.48). The estimated mean percentage changes from baseline to week 96 in trunk fat and VAT for all subjects were 28% and 19%, respectively (both p <0.001). No statistically significant differences were seen in mean percentage change in trunk fat, VAT or VAT:TAT between the NRTI arms (combining third drugs) by intent-to-treat or as-treated analyses (all p ≥0.28). Comparing ATV/r with EFV (combining NRTI), the estimated mean percentage change from baseline to 96 weeks in trunk fat was higher for ATV/r (36.5% vs 21.1%; p = 0.028 in intent-to-treat and 38.9% vs 21.7%; p = 0.028 in as-treated); estimated mean percentage change in VAT tended to be higher for ATV/r vs EFV (26.6% vs 12.4%; p = 0.09 in intent-to-treat and 30.0% vs 14.5%; p = 0.10 in as-treated); however, estimated mean percentage changes in VAT:TAT were similar for ATV/r and EFV (-2.24% vs -1.00%; p = 0.67 in intent-to-treat and -0.43% vs -0.40%; p = 0.99 in as-treated, respectively). The results were similar for absolute changes in trunk fat, VAT and VAT:TAT.
Conclusions: Compared to EFV, patients assigned to ATV/r had significantly larger mean percentage increases in trunk fat, and a trend toward higher mean percentage increase in VAT. However mean changes in VAT:TAT were similar. Similar increases in trunk fat and VAT were seen between ABC/3TC and TDF/FTC arms.
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