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ACTG 5211: phase II study of the safety and efficacy of vicriviroc (VCV) in HIV-infected treatment-experienced subjects: 48 week results
Presented by Roy Gulick, United States.
Gulick R.1, Su Z.2, Flexner C.3, Hughes M.2, Skolnik P.4, Godfrey C.5, Wilkin T.1, Gross R.6, Krambrink A.2, Coakley E.7, Greaves W.8, Zolopa A.9, Hirsch M.10, Kuritzkes D.10, ACTG 5211 Team
1Weill-Cornell Medical College, New York, United States, 2Harvard School of Public Health, Boston, United States, 3Johns Hopkins University, Baltimore, United States, 4Boston University Medical Center, Boston, United States, 5Division of AIDS, NIH, Bethesda, United States, 6University of Pennsylvania, Philadelphia, United States, 7Monogram Biosciences, Inc., South San Francisco, United States, 8Schering-Plough Research Institute, Kenilworth, United States, 9Stanford University, Palo Alto, United States, 10Harvard Medical School, Boston, United States
Background: CCR5 inhibitors demonstrate short-term antiretroviral activity.
Methods: Randomized 48-week study of vicriviroc in treatment-experienced subjects taking ritonavir-containing regimens with R5 virus (Trofile assay, Monogram Biosciences) and HIV-1 RNA (VL) >5000 copies/ml. Vicriviroc at 5, 10, or 15 mg daily or placebo was added to the failing regimen for 14 days; then background antiretrovirals were optimized. Virologic failure was defined as confirmed VL <1 log10 copies/ml below baseline at/after week 16; post-failure crossover to VCV was permitted. The 5 mg dose (n=30) was discontinued early following recommendation from the Study Monitoring Committee and the study was unblinded following reports of 5 malignancies. All analyses are intent-to-treat.
Results: 118 subjects were randomized (8% women; 34% non-whites) with median VL 36380 (4.56 log10) copies/ml and CD4 146 cells/uL.
| VCV dose | 10 mg (n=30) | 15 mg (n=30) | placebo (n=28) | | weeks of f/u (median) | 48 | 48 | 25 | | number of subjects discontinuing treatment early (n, %) | 11 (37%) | 9 (30%) | 23 (82%) | | number of subjects with virologic failure (n, %) | 8 (27%) | 10 (33%) | 24 (86%) | | median HIV-1 RNA change (log10 copies/ml[IQR]) at week 48 | -1.92 [-3.06, -0.92] | -1.44 [-2.54, -0.62] | not done (only 5 pts at week 48) | | proportion with HIV-1 RNA <400/<50 copies/ml at week 48 | 57% / 37% | 43% / 27% | 14% / 11% | | median CD4 count change (cell/uL [IQR])at week 48 | +130 [+45, +183] | +96 [+27, +218] | not done (only 5 pts at week 48) | | co-receptor changes (R5 to D/M or X4; n) | 4 | 3 | 3 (2 after crossover to VCV) |
Of 20 subjects on VCV 10/15 mg with VL <50 copies/ml at 24 weeks, 14 (70%) continued <50 copies/ml at 48 weeks. Of 26 VCV subjects with R5 virus who experienced virologic failure, 9 (35%) had D/M or X4 virus. Grade 3/4 adverse events were similar across arms. 8 malignancies were previously reported (6 in the VCV arms; 2 in the placebo arm, 1 following VCV crossover); no new malignancies occurred.
Conclusions: In treatment-experienced patients, VCV (10/15 mg) demonstrated potent virologic suppression, sustained over 48 weeks. These are the longest available follow-up data with a CCR5 inhibitor-based regimen.
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