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Abstract
ACTG 5211: phase II study of the safety and efficacy of vicriviroc in HIV-infected treatment-experienced subjects
Gulick R.1, Su Z.2, Flexner C.3, Hughes M.2, Skolnik P.4, Godfrey C.5, Greaves W.6, Wilkin T.1, Gross R.7, Coakley E.8, Zolopa A.9, Hirsch M.10, Kuritzkes D.10, for the ACTG 5211 Study Team
1Cornell University, New York, United States, 2Harvard School of Public Health, Boston, United States, 3Johns Hopkins University Hospital, Baltimore, United States, 4Boston University Medical Center, Boston, United States, 5Division of AIDS, NIH, Bethesda, United States, 6Schering-Plough Research Institute, Kenilworth, United States, 7University of Pennsylvania School of Medicine, Philadelphia, United States, 8Monogram Biosciences, Inc., South San Francisco, United States, 9Stanford University, Palo Alto, United States, 10Harvard Medical School, Boston, United States
Background: Vicriviroc is an investigational CCR5 inhibitor with potent short-term antiretroviral activity.
Methods: Double-blind, randomized, 48-week study of vicriviroc in treatment-experienced patients taking ritonavir-containing regimens with R5-tropic virus (Monogram assay) and HIV-1 RNA (VL) >5000 copies/ml. Vicriviroc at 5, 10, or 15 mg daily (or placebo) was given 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 cross-over to vicriviroc was permitted. Primary endpoint was change in VL at day 14. The 5 mg dose was discontinued early following recommendation from the Study Monitoring Committee and the study was unblinded following reports of 5 malignancies. Data for blinded study period are presented; open-label follow-up continues.
Results: 118 patients were randomized (8% women; 34% non-whites) with median VL 36380 (4.56 log10) copies/ml and CD4 146 cells/uL.
HIV-1 RNA decrease was greater in each vicriviroc group than placebo at day 14 and week 24 (P<.01) and not different between vicriviroc groups (P>.05)(ITT). Grade 3/4 adverse events were similar across groups. Among vicriviroc patients, 2 developed Hodgkin´s disease (HD)(one with prior HD); 2 non-Hodgkin´s lymphoma (one with prior HD); and 1 gastric adenocarcinoma.
Conclusions: In treatment-experienced patients, vicriviroc demonstrated potent 14-day virologic suppression and, following optimization of background antiretrovirals, sustained antiretroviral activity over 24 weeks. The relationship of vicriviroc to malignancy is uncertain.
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