Ibalizumab (IBA) is a CD4-directed post-attachment HIV-1 inhibitor that binds to the CD4 domain 2 and blocks viral entry into host cells without immunosuppression. Here, we report the efficacy outcomes of IBA with OBR in patients resistant and susceptible to two widely used antiretrovirals (ARV), dolutegravir (DTG) and darunavir (DRV) as well as the the long-term safety and efficacy through 96 weeks of treatment.
In TMB-301, heavily treatment-experienced patients with MDR HIV-1 received an intravenous loading dose of 2000 mg followed by 800 mg doses every 2 weeks up to Week 25. An OBR with at least 1 additional sensitive agent was added 7 days after the loading dose. Following completion of the TMB-301 study, eligible patients continued to receive IBA at 800 mg every 2 weeks under TMB-311 for up to 96 weeks.
Among the 40 enrolled patients in TMB-301, 18 (45%) had DTG resistance, of which 11 had major DTG resistance mutations (Q148 plus additional mutations). Of 18 DTG resistant patients, 10 received DTG in their OBR while 16 of 22 DTG susceptible patients received DTG as OBR. Twenty-seven patients (68%) had DRV resistance. DRV was included as OBR in 26 patients: 18 with DRV resistant HIV and 8 with DRV susceptible HIV. Long-term results were obtained for 27 patients who continued to receive treatment in study TMB-311, of which 22 (82%) completed treatment up to 96 weeks. The reasons for 5 discontinuations were death (2 patients) consent withdrawal (2 patients) and physician decision – all 5 were non IBA-related. IBA plus OBR was well tolerated with no new safety concerns emerging between Week 25 and 96. For these 27 patients, median viral load (VL) reduction from Baseline (of TMB-301) was 2.5 log10 at Week 25 and 2.8 log10 at Week 96 in the Intent-to-Treat-Missing-Equals-Failure analysis. Of 16 patients with HIV RNA <50 copies/mL at Week 25, 14 maintained viral suppression through Week 96, with one additional patient achieving viral suppression by Week 96. Median CD4+ T cell increase was 42 cells/µl from Baseline to Week 25 (n=27), and 45 cells/µl at Week 96 among those who remained on study (n=22).
Safety and efficacy of IBA observed at Week 25 in the Phase 3 trial were maintained through 96 weeks for patients continuing on treatment. IBA is an effective, safe and durable treatment for MDR HIV-1 infected patients.