H-1030

289

Two-Year Follow-Up of Treatment-Experienced Patients on Vicriviroc (VCV)

CCR5,clinical trial

R. GULICK¹, D. HAAS ², A. C. COLLIER ³, J. LENNOX ⁴, C. PARKER ⁵, W. GREAVES ⁵;
¹Weill-Cornell Med. Coll., New York, NY, ²Vanderbilt Univ., Nashville, TN, ³Univ. Washington, Seattle, WA, ⁴Emory Univ., Atlanta, GA, ⁵Schering Plough, Kenilworth, NJ.

  R. Gulick, Gilead; Merck; Panacos; Pfizer; Schering; Tibotec; Abbott; Bristol Myers; Gilead; GlaxoSmithKline; Koronis (DSMB member); Merck; Monogram; Pfizer; Roche-Trimeris; Schering; Tibotec; Virco.

Background: VCV demonstrated durable antiretroviral activity and CD4 response in treatment-experienced (TE) subjects at 48 weeks (Gulick, IAS 2007 abstract 1623). We present 2-year data for TE patients who received VCV and participated in a roll-over study. Methods: HIV-1 infected subjects successfully completing the 48-week phase of ACTG 5211 could enter this open-label multicenter study and receive VCV 15 mg in addition to previously optimized background therapy (OBT) that included a ritonavir-boosted protease inhibitor. Additionally, subjects with a tropism shift to R5/X4 virus with HIV RNA ≥1 log₁₀ below baseline and no decrease in CD4 count could enroll. We assessed change from baseline in HIV RNA and CD4 in subjects who had ≥12 months follow-up, as well as new opportunistic infections (OIs); malignancies; seizures; and hepatotoxicity. Results: Of 79 subjects entering the study, 54 had at least 12 months exposure to VCV. Data were available for 39 subjects (data pending for 15 ongoing subjects): mean treatment duration (from first dose in ACTG 5211 to last dose in the rollover protocol) was 103 weeks (range 49-145). Median change in HIV RNA from baseline (ACTG 5211) was -2.2 log₁₀; median change in CD4 count was +84 cells/mm³; 23/39 subjects (60%) had HIV-RNA <50 copies/mL and 28/39 (72%) had <400 copies/mL. 12 subjects discontinued: 2 due to adverse events, 6 for patient choice, 2 for administrative reasons, and 2 for virologic failure. 6 tropism shifts occurred during the study: 2 to X4 and 4 to R5/X4. Other than pulmonary TB (n=1), no OIs, VCV-related hepatotoxicity, cardiovascular events, seizures, or new lymphomas (since February 2006) were reported. Conclusions: VCV, 15 mg qd, plus OBT was generally well tolerated and provided potent and durable antiretroviral activity. These results represent the longest follow-up data available for a CCR5-containing regimen to date.