|
14th Conference on Retroviruses and Opportunistic InfectionsLos Angeles, California - February 25-28, 2007 |
Conf Retrovir Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 38)
Richard H. Haubrich
1, S Riddler2, G DiRienzo3, L Komarow3, W Powderly4, K Garren5, T George6, J Rooney7, J Mellors2, D Havlir8, and the AIDS Clinical Trials Group 5142 Study Team
1Univ of California, San Diego, US; 2Univ of Pittsburgh, PA, US; 3Harvard Sch of Publ Hlth, Statistical and Data Analysis Ctr, Boston, MA, US; 4Univ Coll Dublin, Ireland; 5Abbott Labs, Abbott Park, IL, US; 6Bristol-Myers Squibb, Plainsboro, NJ, US; 7Gilead Sci, Foster City, CA, US; and 8Univ of California, San Francisco, US
BACKGROUND: The metabolic effects of lopinavire (LPV)- or efavirenz (EFV) -based regimens + 2 nucleoside reverse transcriptase inhibitors (NRTI) have not been compared nor has the role of an NRTI-sparing regimen in preventing lipoatrophy been tested.
METHODS: This open-label, randomized trial compared class-sparing regimens for naïve subjects: LPV+EFV vs LPV+2 NRTI (LPV soft-gel twice daily) vs EFV+2 NRTI. NRTI were selected before randomization from zidovudine (ZDV), stavudine (d4T XR), or tenofovir (TDF) (each plus lamivudine [3TC]). Metabolic objectives included evaluation of changes in fat (DEXA) and fasting lipids. DEXA and lipids were performed at baseline, and 48 and 96 weeks. Lipoatrophy was defined as ≥20% loss of limb fat from baseline. All analyses were intent to treat without adjustment for multiple comparisons or regimen changes. Pairwise comparisons used non-parametric tests.
RESULTS: We enrolled 753 subjects (median CD4 182 cells/mm3, median HIV-1 RNA 100,000 copies/mL) who were followed for a median 112 weeks. The NRTI of choice was ZDV 42%, d4T XR 24%, and TDF 34%. Median baseline values were not different by arm: trunk fat 8.2 kg, extremity fat 7.0 kg, total cholesterol (TC) 154 mg/dL, HDL 35 mg/dL, non-HDL 117 mg/dL, and triglycerides (TG) 116 mg/dL. By week 96, 10%, 12%, and 26% of EFV, LPV, and LPV/EFV subjects used a lipid-lowering agent. Week-96 results (see the table) were similar to other time points. Lipoatrophy in the EFV or LPV+NRTI was predominately seen in the d4T- or ZDV-containing regimens; there was no significant difference (p >0.5) in lipoatrophy between TDF- containing and NRTI-sparing regimens.
| Week 96 Result | Primary Randomized Arm | ||||
| N | EFV | LPV | LPV/EFV | p ≤ 0.01 | |
| Median value or % | |||||
| % D extremity fat | 498 | 0.3 | 9.9 | 18 | a,b,c |
| % D trunk fat | 498 | 12 | 19 | 17 | -- |
| lipoatrophy | 498 | 32% | 18% | 8% | a,b,c |
| D TC (mg/dL) | 517 | 33 | 33 | 57 | b,c |
| D HDL (mg/dl) | 508 | 9 | 8 | 16 | b,c |
| D non-HDL (mg/dL) | 506 | 21 | 26 | 43 | b,c |
| D TG (mg/dL) | 518 | 14 | 47 | 63 | a,b*,c |
| NRTI (LPV and EFV Arms) | ||||
| N | d4T | TDF | ZDV | p ≤ 0.05 |
| Median value or % | ||||
| 329 | –11 | 17 | 2.0 | d,e,f |
| 329 | 11 | 23 | 16 | d |
| 329 | 43% | 10% | 27% | d,e,f |
| 343 | 41 | 21 | 33 | d |
| 334 | 8 | 8 | 9 | -- |
| 333 | 26 | 17 | 26 | d |
| 344 | 47 | 21 | 24 | d |
| Pairwise comparisons: a = EFV vs LPV; b = LPV vs LPV/EFV; c = EFV vs LPV/EFV; d = d4T vs TDF; e = TDF vs ZDV; f = ZDV vs d4T. b*= 0.025. If not listed, p >0.05 |
CONCLUSIONS: A NRTI-sparing regimen (LPV+EFV) increased lipids significantly more than EFV or LPV+2 NRTI regimens. Triglyceride increases were also greater in LPV compared to EFV+NRTI regimens, but cholesterol changes were not significantly different. Compared to EFV, LPV had less lipoatrophy when given with NRTI. The frequency of lipoatrophy was lowest in NRTI-sparing and TDF-containing regimens.
2007-02-25
38
Copyright © 2007 - 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.
Download abstract