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HIV Control With Ibalizumab for 7.8 to 9.5 Years With Few Regimen Tweaks
  IDWeek 2020, October 22-25, 2020
Mark Mascolini
All 12 people taking a rescue regimen based on every-2-week infused ibalizumab (Trogarzo) in an expanded-access program maintained a viral load below 200 copies through their last follow-up visit [1]. After 7.8 to 9.5 years of ibalizumab therapy, the initial optimized background regimen required additional antiretrovirals in only 4 people, 2 of whom added only a ritonavir booster.
Ibalizumab, a monoclonal antibody that thwarts HIV entry into CD4 cells [2], is licensed for adults with multidrug-resistant HIV whose current regimen is failing. Treatment requires an intravenous loading dose of 2000 mg followed every 2 weeks by 800-mg infusions.
The TMB-202 trial involved 113 people with multidrug-resistant HIV who received either 2000 mg of ibalizumab every 4 weeks of 800 mg every 2 weeks for 24 weeks with an optimized background regimen [3]. Fifty-six of 96 people who completed TMB-202 entered an investigational new drug protocol, and 12 of those 56 later enrolled in an expanded-access protocol, TMB-311 [4], which continued until FDA licensing of ibalizumab in March 2018. This report focuses on those 12 people.
All 12 study participants were men, and 11 were white. Median baseline age stood at 55 years, and median HIV duration at 22 years. Before ibalizumab therapy began, median viral load measured 4.4 log10 copies/mL (about 25,000 copies), and median CD4 count was 135. At the end of TMB-202, 11 of these 12 people had a viral load below 200 copies, and 8 of 12 had a sub-50-copy load. All 12 people had a viral load below 200 copies at their last TMB-311 visit (at weeks 108 to 124), and 11 of 12 had a load below 50 copies.
Average CD4 count climbed from 135 before ibalizumab began, to 199 in the 12 study participants after week 25 of TMB-202, and to 234 at week 96 of TMB-311.
No one withdrew from treatment or was lost to follow-up during TMB-311. Two people died of causes not related to treatment, injury and metastatic tonsil cancer. The researchers recorded no treatment-emergent adverse events related to ibalizumab during follow-up. Five people had a serious adverse event, 6 had a severe treatment-emergent adverse event, but no one had a treatment-emergent adverse event related to study drug or leading to stopping ibalizumab.
Throughout these ibalizumab studies, the 12 study participants continued taking ibalizumab for 7.8 to 9.5 years (average 8.9 years). During that time 8 people (67%) needed no additional drugs in their ibalizumab regimen. Among the 4 people who added drugs, 2 added only a ritonavir booster. Two people simplified their regimen during follow-up.
The TMB-311 investigators believe their findings "demonstrate the durability of viral suppression when combining the long-acting antiretroviral ibalizumab with short-acting oral agents" and that long-term ibalizumab-based combinations are safe and tolerable.
1. Towner W, DeJesus E, Schrader S, et al. Long-term efficacy, safety, and durability of ibalizumab-based regimens in subgroup of TMB-202 participants. IDWeek 2020, October 22-25, 2020. Abstract 1027.
2. Beccari MV, Mogle BT, Sidman EF, Mastro KA, Asiago-Reddy E, Kufel WD. Ibalizumab, a novel monoclonal antibody for the management of multidrug-resistant HIV-1 infection. Antimicrob Agents Chemother. 2019;63:e00110-19. doi: 10.1128/AAC.00110-19. https://aac.asm.org/content/aac/63/6/e00110-19.full.pdf
3. ClinicalTrials.gov. Dose-response study of ibalizumab (monoclonal antibody) plus optimized background regimen in patients with HIV-1 (TMB-202). ClinicalTrials.gov identifier NCT00784147. https://clinicaltrials.gov/ct2/show/NCT00784147
4. ClinicalTrials.gov. Ibalizumab plus optimized background regimen in treatment-experienced patients with multi-drug resistant HIV-1. ClinicalTrials.gov identifier NCT02707861. https://clinicaltrials.gov/ct2/show/NCT02707861