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12th Conference on Retroviruses and Opportunistic InfectionsBoston, Massachusetts - February 22-25, 2005 |
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Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 45LB
Robert Murphy1
, J Zhang2, R Hafner3, A Shevitz4, K Tashima5, K Yarasheski6, J Forand4, B Berzins1, S Owens7, S Evans2, P Tebas8, and AACTG 5110 Study Team
1 Northwestern Univ, Chicago, IL, USA; 2 Harvard Sch of Publ Hlth, Boston, MA, USA; 3 NIAID, NIH, DHHS Bethesda, MD, USA; 4 Tufts Univ Sch of Med, Boston, MA, USA; 5 Brown Univ, Providence, RI, USA; 6 Washington Univ, St Louis, MO, USA; 7 Frontier Sci Technology Res Fndn, Amherst, NY, USA; and 8 Univ of Pennsylvania, Philadelphia, USA
BACKGROUND: Options for patients (patients) with peripheral lipoatrophy are limited. The MITOX and TARHEEL studies demonstrated that switching from a thymidine analog partially reversed lipoatrophy. ACTG 5125s showed that switching to a nucleoside reverse transcriptase inhibitor (NRTI) sparing regimen increases peripheral fat. We evaluated both interventional approaches and no treatment change.
METHODS: Patients at 15 ACTG sites receiving thymidine analogs stavudine (d4T) or zidovudine (ZDV) containing regimens with HIV RNA ≤ 500 copies/mL and clinical evidence of peripheral lipoatrophy were prospectively randomized to: switch thymidine analog to abacavir (ABC); discontinue all ART and switch to lopinavir/ritonavir (LPV/r) plus nevirapine (NVP), a regimen without NRTI; 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 48 weeks post-intervention.
RESULTS: Of the 101 patients enrolled (85% men, 69% white), 77 switched immediately and 24 delayed. Median age was 46 years, CD4 = 611 cells/mm3, viral load < 200 copies/mL = 96%; 76% were on d4T and 24% were on ZDV. Baseline median (IQR) subcutaneous thigh fat was 18.9 (8.3 to 29.2) cm2, 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) ratio 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. There were significant SAT increases and VAT:TAT decreases for both interventions and a decrease VAT for ABC. Between group comparisons were significant for SAT and VAT:TAT. There was a significant increase in CD4 for LPV/r+NVP.
| Treatment arm (n) | Subcutaneous thigh fat | SAT | VAT | VAT:TAT | CD4 | % Viral load < 200 copies |
| LPV/r+NVP (37) | + 8.4* | + 16.6 **† | – 15.0 | –9.0**†† | +8.0# | 93 |
| ABC (40) | –0.2 | + 9.2 ***† | –15.3** | –11.7**†† | –4.8 | 92 |
| Delayed switch (24) | –3.2 | –8.8† | –2.8 | +4.3†† | +2.4 | 100 |
| Change within arm p = 0.06*, p < 0.01**, p = 0.04***, p = 0.03#; Difference between arms p = 0.008†, p < 0.001†† |
CONCLUSIONS: In patients with lipoatrophy, switching d4T or ZDV to a nonthymidine analog or changing to a NRTI-sparing regimen is associated with significant improvements in SAT, VAT, and VAT:TAT while maintaining virologic control and improving CD4 with NRTI-sparing. Further follow-up is needed to identify long-term effects.
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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.
