CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

450LB A PHASE 2 OPEN-LABEL TRIAL OF ANTIBODY UB-421 MONOTHERAPY AS A SUBSTITUTE FOR HAART Chang-Yi Wang 1 , Wingwai Wong 2 , Hung-Chin Tsai 3 , Yen-Hsu Chen 4 , Mei-June Liao 5 , Shugene Lynn 6 , for the United BioPharma UB-421 Clinical and ResearchTeam 1 United Biomed, Inc, Hauppauge, NY, USA, 2 Taipei Veterans General Hosp, Taipei, Taiwan, 3 Kaohsiung Veterans General Hosp, Kaohsiung, Taiwan, 4 Kaohsiung Med Univ and Hosp, Kaohsiung, Taiwan, 5 United Biopharma, Inc, Hsinchu, Taiwan, 6 UBI Asia, Hsinchu, Taiwan Background: The antiviral activity of UB-421, a monoclonal antibody that binds to CD4 receptor to block HIV-1 entry, was demonstrated in a prior Phase 2a trial of 29 antiretroviral-naïve HIV-1(+) adults in Taiwan (Trial No. NCT01668043); the average (and SD) of maximum viral load (VL) reduction was 2.27 (0.6) and 2.45 (0.46) log10 copies/mL after 8-week monotherapy on 10mg/Kg/weekly or 25mg/Kg/biweekly, respectively. Methods: Efficacy and safety of UB-421 monotherapy was examined in this Phase 2 trial among HAART-stabilized HIV-1(+) Asian adults whose VLs had been recorded as undetectable (< 50 copies/mL) at least twice in the past year (NCT02369146); 14 and 15 such adults interrupted HAART to receive 8 doses of UB-421 infusions on 10mg/Kg/weekly (Arm 1) or 25mg/Kg/biweekly (Arm 2) regimens, respectively, with prompt return to HAART if viral rebound (VR, > 400 copies/mL at 2 consecutive visits). Efficacy was assessed as the percentage of and the time to VR; changes in laboratory parameters were compared to baseline. Results: Twenty-seven of 29 enrolled subjects completed all 8 doses of UB-421 with no VR during the monotherapy period, which was 8-week for Arm 1 and 16-week for Arm 2. Two subjects in Arm 2 did not complete (1 lost to follow-up, 1 withdrew due to skin rash), but had undetectable VL for all trial visits. At the end of treatment (EOT), 22 subjects resumed HAART and were monitored for 8 weeks with continuous viral suppression. Five subjects (3 in Arm 1 and 2 in Arm 2) refused to resume the scheduled HAART, and viral rebound was detected 35-62 days after the last UB-421 dose; all 5 re-started HAART right after rebound, and their VL were monitored until undetectable. At the end of study for both arms, CD4+ T cell counts remained stable (p>0.17 Wilcoxon signed-rank (WSR) test), while CD8+ T cell counts increased (p<0.05). The 27 completers exhibited significant reductions (interquartile =1.7% - 3.1%) of CD4+ T regulatory cell percentage at EOT (p<0.001 WSR test). In 11 subjects with proviral DNA > 100 copies/10 6 PBMC at baseline, 10 showed a mean 2.24-fold reduction at EOT. The most common drug-related (possible or probable) adverse event (AE) was mild to moderate skin rash (48.3% of 29 subjects), and no death or drug-related SAE occurred. Conclusion: No viral rebound occurred during the UB-421 monotherapy period; the regimen was safe and well tolerated. UB-421 warrants further evaluation for an indication as monotherapy for HAART substitution in virally suppressed HIV-1 adults. 451LB DOLUTEGRAVIR AS MAINTENANCE MONOTHERAPY FOR HIV-1: A RANDOMIZED CLINICAL TRIAL Ingeborg Wijting 1 , Casper Rokx 1 , Charles Boucher 1 , Dorine de Vries - Sluijs 1 , Karin Schurink 1 , Elrozy Andrinopoulou 1 , Eric van Gorp 1 , Wouter Bierman 2 , Bart Rijnders 1 , for the DOMONO Study-Group 1 Erasmus Univ Med Cntr Rotterdam, Rotterdam, Netherlands, 2 Univ Med Cntr Groningen, Groningen, Netherlands Background: The development of integrase (IN) inhibitor resistance during dolutegravir (DTG) containing cART is exceedingly rare. This high genetic resistance barrier may make DTG suitable as maintenance monotherapy. We hypothesized that DTG monotherapy is non-inferior to cART in maintaining viral suppression. Methods: Multicenter randomized trial comparing DTG 50mg QD (DOLUMONO) with continued cART(con-cART). Pts included were HIV-1+ and on cART with a viral load (VL)<50c/ ml for >6months, a CD4 nadir >200cells/ul, a pre-cART peak VL<100.000c/ml and no history of virological failure (VF). 24wks after randomization, the con-cART group switched to DOLUMONO as well (delayed switch), fig1. The primary endpoint was the on-treatment proportion of pts with a VL<200c/ml at W24. Assuming 95% viral suppression, 104 pts were needed for a study with β=80%, δ=-0.12, and α=0.025. Secondary endpoints were VL<200c/ml and <50c/ml at W24 and W48 in all pts on DOLUMONO (immediate+delayed switch group combined). Due to the “W24 delayed switch” study design, no randomized con-cART control group is available to compare the W48 DTG monotherapy results with. Therefore, a concurrent control group of 152 pts on cART was included (fig1). These pts fulfilled the same in -and exclusion criteria but continued their cART. NCT02401828. Results: 104 pts were included and on cART for 40 months with CD4 nadir of 340cells/ul. One pt discontinued DTG at W12 for adverse events. At W24, DOLUMONO was non- inferior to con-cART: VL<200c/ml in 49/50 vs 53/53 (Δ2%, Exact 95%CI +12% to -5%) with no IN resistance in the single VF. Also 46 of 53 pts randomized to con-cART switched to DOLUMONO 24 weeks after randomization. Consequently, a total of 96 pts received DTG monotherapy, of whom 94 have reached W24. 92/94 had a VL<200c/ml with no resistance in the 2 VF. However, when 77 of the 96 pts had reached W48 of monotherapy, VF had developed in 8 (2 before W24, 6 after W24). IN genotyping was successful in 6 and resistance found in 3: the 155H and 263K in 1 pt each and the 230R, a mutation not previously described during DTG therapy, in 1 pt. As per predefined stopping rule, this led to the premature study discontinuation. In the concurrent control group on cART, VF was observed significantly less (3/152 vs 8/96, p=0.03). Conclusion: Although DTG monotherapy was non-inferior to cART at W24, VF continued to occur after W24 and led to DTG resistance in 3. The genetic barrier of DTG monotherapy is insufficient to allow for maintenance monotherapy.

Poster and Themed Discussion Abstracts

CROI 2017 188