CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Methods: The CrossMab technology was used to construct a library of bispecific Abs. One potent and broad Ab, 10E8 V2.0 CD4 receptor using ibalizumab (iMab) and the other arm targeting gp41 using a modified 10E8 (10E8 V2.0 human hematopoietic cells. First, mice infected with HIV JR-CSF received weekly injections of 0.5 mg 10E8 V2.0 gp120 engineered Ab. Second, uninfected mice receiving weekly injections of 0.2 mg 10E8 V2.0

/iMab, was identified, with one arm targeting the human

). We then evaluated its in vivo efficacy in NSG mice reconstituted with /iMab for 7 weeks, alone or in combination with 0.5 mg of an anti- /iMab were challenged 3 times intraperitoneally with JR-CSF to assess its protective

efficacy. In both experiments, viral RNA in plasma was assessed weekly. Results: 10E8 V2.0 /iMab showed breadth of 100% against a panel of 118 HIV strains, with mean IC 50 and IC 80 reduced the virus load by 1.7 log in infected mice after 2 weeks of treatment (Mann-Whitney test, p < 0.001 vs iMab + 10E8 V2.0 was associated with mutations in the 10E8 epitope, implying that its antiviral activity was mainly mediated by the 10E8 V2.0 V2.0 /iMab and an anti-gp120 Ab led to a sustained viral load decrease of 2.3 log during the course of treatment. 10E8 V2.0 in humanized mice against three systemic HIV challenges, whereas 16/19 saline-treated mice became infected after one challenge (log rank test, p = 0.0001). Conclusions: 10E8 V2.0 /iMab appears to be the most potent HIV-neutralizing Ab described to date. Moreover, it has shown unprecedented activity for an Ab in both treating and preventing HIV in a humanized mouse model. 10E8 V2.0 /iMab thus holds promise as a novel prophylactic and therapeutic agent in the fight against HIV. 10E8 V2.0 /iMab could potentially serve as an anchor for a combination of antibodies to treat HIV on a monthly basis. of 0.002 ug/mL and 0.006 ug/mL, respectively. In vivo, this Ab alone co-administration). Subsequent viral rebound arm that is concentrated at the site of viral entry. The combination of 10E8 /iMab also provided complete protection

470 Doravirine 100mg QD vs Efavirenz +TDF/FTC in ART-Naive HIV+ Patients: Week 48 Results

Josep María Gatell 1 ; Francois Raffi 2 ; Andreas Plettenberg 3 ; Don Smith 4 ; Joaquin Portilla 5 ; Christian Hoffmann 6 ; Keikawus Arasteh 7 ; MelanieThompson 8 ; Xia Xu 9 ; HedyTeppler 9 1 Hosp Clínic de Barcelona, Barcelona, Spain; 2 Chu Hotel Dieu-Chu De Nantes, Nantes, France; 3 IFI Inst for Interdisciplinary Med, Hamburg, Germany; 4 Albion Cntr, Sydney, Australia; 5 Univ Miguel Hernandez, Alicante, Spain; 6 IPM StudyCntr, Hamburg and Univ of SchleswigHolstein, Campus Kiel, Hamburg, Germany; 7 EPIMED/Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany; 8 AIDS Rsr Consortium of Atlanta, Atlanta, GA, USA; 9 Merck & Co, Inc, Kenilworth, NJ, USA

Background: Doravirine (DOR), an investigational NNRTI with a novel resistance profile, was compared with efavirenz (EFV) in a randomized, double-blind, 2-part study in ART-naïve HIV-infected patients also receiving tenofovir/emtricitabine (TDF/FTC). Part 1 evaluated DOR 25, 50, 100, and 200 mg once daily and EFV 600 mg once daily; based on week 24 results, DOR 100 mg once daily was selected for ongoing evaluation. Part 2 enrolled additional patients to receive DOR 100 mg or EFV. At week 24 (Parts 1+2 combined), DOR 100 mg demonstrated antiretroviral activity and immunological effect similar to EFV (each with TDF/FTC) with significantly fewer CNS adverse events. Data through week 48 are now available from this ongoing study. Methods: Week 48 data from patients who received DOR 100 mg or EFV in Part 1 (n=42 per group) and Part 2 (n=66 per group) were combined for this analysis. Patients were stratified at randomization by screening HIV RNA ≤ or >100,000 copies/mL. The primary efficacy endpoint is the proportion of patients with HIV RNA <40 copies/mL, using the non-completer=failure approach. Results: 216 patients (93%male, 80%white, mean age 36 years) were randomized and treated. Mean baseline HIV RNA was 4.6 log 10

Poster Abstracts

copies/mL in both the DOR and EFV groups, and mean CD4 counts were 432 and 448 cells/mm 3 , respectively. 88% of the DOR group and 85% of the EFV group completed 48 weeks of treatment. Reasons for discontinuation included adverse event (n=3 on DOR, 6 on EFV), lack of efficacy (0, 1), and other reasons (10, 9). Efficacy and safety results are shown in the table below. Drug-related AEs with incidence >5% in either treatment group were diarrhea (DOR 0.9%, EFV 6.5%), nausea (7.4%, 5.6%), dizziness (6.5%, 25.9%), headache (2.8%, 5.6%), abnormal dreams (5.6%, 14.8%), insomnia (6.5%, 2.8%), nightmares (5.6%, 8.3%), and sleep disorder (4.6%, 6.5%). There were no discontinuations due to drug-related AEs after week 24. Laboratory abnormalities ≥Grade 2 were uncommon in both groups. Conclusions: DOR 100 mg once daily demonstrated antiretroviral activity and immunological effect similar to EFV (each with TDF/FTC) and was generally safe and well tolerated during 48 weeks of treatment in ART-naïve, HIV-1 infected patients. Drug-related AEs were significantly less frequent in the DOR group compared with the EFV group.

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