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Switching to Thymidine Analogue Sparing or Nuke Sparing Regimen improves Lipoatrophy: 24 week results of a prospective randomized clinical trial, AACTG 5110
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Reported by Jules Levin
In the same oral Complications session at CROI, immediately following Moyle's report of improved fat loss after switching to TDF or ABC from thymidine analogues AZT & d4T, Rob Murphy reported on a switch study where patients with lipoatrophy switched to either an abacavir based regimen (off AZT or d4T) or switched off ART & onto a NRTI-sparing regimen of lopinavir/ritonavir (Kaletra plus nevirapine.
Patients at 15 ACTG sites receiving thymidine analogues d4T or AZT containing regimens with HIV RNA <500 copies/ml and clinical evidence of peripheral lipoatrophy were prospectively randomized to: switch thymidine analogues to abacavir (ABC); discontinue all ART and switch to lopinavir/ritonavir plus nevirapine, a regimen without NRTIs; or delay switching for 24 weeks. Centrally analyzed single-slice CT of mid-thigh and abdominal fat, metabolic and virologic/immunologic parameters were measured at baseline and week 24 as the primary endpoint. At week 24, the delayed switch group began their intervention. All patients were followed for 48 weeks post-intervention.
Of the 101 patients enrolled (85% men, 69% white), 77 switched immediately and 24 delayed. Median age was 46, CD4=611, viral load <200 copies/ml=96%; 76% were on d4T & 24% on AZT. Baseline median subcutaneous fat was 18.9 (8.3 to 29.2), subcutaneous abdominal adipose tissue (SAT) 74.2 (44.6 to 122.5) cm2, visceral adipose tissue (VAT) 116.3 (69.8 to 176.8) cm2, and VAT:TAT (total adipose tissue) ration 0.58 (0.45 to 0.71). The table shows median percentage changes at 24 weeks. In sum, at 24 weeks subcutaneous thigh fat increased in the LPV/r + NVP group, but not in the ABC group. There were significant SAT increases & VAT:TAT decreases for both interventions and a decrease VAT for ABC. Between group comparisons were significant for SAT & VAT:TAT. There was a significant increase in CD4 for LPV/r+NVP.
Murphy concluded that in patients with lipoatrophy, switching d4T or AZT to a non-thymidine analogue or changing to a NRTI-sparing regimen is associated with significant improvements in SAT, VAT, & VAT:TAT while maintaining virologic control & improving CD4 with NRTI-sparing. Further follow-up is needed to identify long-term effects. In speaking with Murphy after his talk I asked about the no improvement in thigh fat seen with use of ABC & he was only able to suggest that perhaps there is discordant response between different areas of the body.
| TREATMENT ARM | Subc Thigh Fat | SAT | VAT | VAT:TAT | CD4 | % VL<200 | | LPV/r+NVP | +8.4* | +16.6 | -15 | -9.0 | +8 | 93 | | ABC | -0.2 | +9.2 | -15.3 | -11.7 | -4.8 | 92 | | Delayed Switch | -3.2 | -8.8 | -2.8 | +4.3 | +2.4 | 100 |
*p=0.06
Changes in SAT, VAT, VAT:TAT were significant.
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