CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

mutations were found in 2 and the K103N NNRTI mutation in 2 cases, one of those retrospectively identified as transmitted mutation at baseline. Neutropenia was overall frequently observed, toxicity grade increases by 3 or 4 grades compared to baseline were significantly more common in the ZDV compared to combined FZD arms (p=<0.001). Grade III/IV anemia was seen only in 2 cases (Arm B with sickle cell trait and arm D). Mean decrease of hemoglobin and neutrophils at early time points were more pronounced in the ZDV as compared to combined FZD arms (p=0.033 and 0.004 resp).

*Grades do not represent absolute toxicity but subtracted grade increase from baseline toxicity grades (ANRS Toxicity Scale, Vers. 1.0, 4th Nov 2008). # p-values from Kruskal-Wallis and Fisher’s exact tests. Conclusions: Virologic 24 weeks efficacy was demonstrated in a FZD based ART regimen. Despite a small sample size evidence for reduced myelotoxicity in FZD compared to ZDV based regimens was seen. PK data for dose finding criteria is pending. 545 Attachment Inhibitor Prodrug BMS–663068 in ARV-Experienced Subjects: Week 48 Analysis Melanie Thompson 1 ; Jay Lalezari 2 ; Richard Kaplan 3 ;Yvette Pinedo 4 ; Otto Sussman Pena 5 ; Pedro Cahn 6 ; David A. Stock 7 ; Samit R. Joshi 7 ; George J. Hanna 8 ; Max Lataillade 7 1 AIDS Research Consortium of Atlanta, Atlanta, GA, US; 2 Quest Clinical Research, San Francisco, CA, US; 3 Desmond Tutu HIV Foundation, Cape Town, South Africa; 4 Asociacion Civil Via Libre, Lima, Peru; 5 Asistencia Cientifica de Alta Complejidad SAS, Bogotá, Colombia; 6 Fundacion Huesped, Buenos Aires, Argentina; 7 Bristol-Myers Squibb, Wallingford, CT, US; 8 Bristol-Myers Squibb, Princeton, NJ, US Background: BMS-663068 is a prodrug of BMS-626529, a first-in-class attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into host CD4+ T-cells. AI438011 is an ongoing Phase 2b, randomized, active-controlled trial investigating the safety, efficacy and dose–response of BMS-663068 vs atazanavir/ ritonavir (ATV/r) in treatment-experienced (TE) HIV-1-infected patients (pts). At Week 24, BMS663068 arms had similar response rates to ATV/r and were generally well tolerated with no BMS-663068-related SAEs or AEs leading to discontinuation (D/C). Here we report the Week 48 results. Methods: TE adults ( ≥ 1 week exposure to ≥ 1 ARV) with viral load (VL) ≥ 1,000 c/mL and susceptibility to all study drugs (including a conservative cut-off for BMS-626529 IC 50 <100 nM) were randomized equally to four BMS-663068 groups (400 or 800 mg BID; 600 or 1200 mg QD) and a control group (ATV/r 300/100 mg QD), each with a background of raltegravir (RAL) 400 mg BID + tenofovir disoproxil fumarate (TDF) 300 mg QD. Efficacy and safety at Week 48 were assessed as secondary endpoints. Results: 254 pts were randomized and 251 were treated across all arms. At baseline (BL), demographics were similar across arms: median age=39 yrs, male=60%, non- white=62%, median BL VL=4.85 log 10 c/mL (43% had VL ≥ 100,000 c/mL), median CD4 count=230 cells/ m L (38% had <200 CD4 cells/ m L). Approximately 50% of pts had ≥ 1 major NRTI, NNRTI or PI resistance-associated mutation at BL. Through Week 48, 61–82% of BMS-663068 pts and 71% of ATV/r pts had HIV-1 RNA <50 c/mL (Table, mITT FDA Snapshot). Similarly, 77–95% of BMS-663068 pts and 88% of ATV/r pts had HIV-1 RNA <50 c/mL in the observed analysis (Table). Mean increase in CD4 counts from baseline were 141–199 cells/ m L across BMS-663068 arms and 179 cells/ m L for the ATV/r arm. Observed virologic response rates across the BMS-663068 and ATV/r arms by BL VL <100,000c/mL were 74–100% vs 96%, respectively and by BL VL ≥ 100,000c/mL were 60–91% vs 71%, respectively. All BMS-663068 doses were generally well tolerated and no BMS-663068-related AEs led to D/C.

Poster Abstracts

Week 48 Efficacy Results

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CROI 2015