What is the role of post-attachment inhibitors in antiretroviral therapy of HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Answer

Answer

The CD4-directed postattachment inhibitor, ibalizumab (Trogarzo), is the first medication approved for this class in March 2018. It is indicated HIV-1 infection in heavily treated adults with multidrug-resistant infection failing their current antiretroviral therapy regimen. It is used in combination with the patient’s current ART regimen.

Approval of ibalizumab was based on the MB-301 phase 3 trial. MB-301 was a single arm, 24-week study of ibalizumab plus optimized background regimen (OBR) in treatment-experienced patients infected with multidrug resistant HIV-1. The primary objective of the study was to demonstrate the antiviral activity of ibalizumab 7 days after the first dose of ibalizumab. Patients receiving their current failing ART, or no therapy, were monitored during a 7-day control period. Thereafter, a single loading dose of ibalizumab 2,000 mg IV was the only ART added to their regimen. The primary efficacy endpoint was the proportion of patients achieving a ≥0.5 log10 decrease in HIV-1 RNA 7 days after initiating ibalizumab therapy, day 14 of the study. Ibalizumab was continued at doses of 800 mg IV every 2 weeks through 24 weeks on study treatment. A total of 40 patients were enrolled in the study. After completion of treatment, patients were offered participation in the expanded access study (TMB-311). The expanded access study was also open for U.S. patients with limited options. [101]

The following study results were observed at 24 weeks: [101]

  • 43% of study participants achieved viral suppression < 50 copies/mm 3 and half < 200 copies/mm 3
  • While 60% of those with a baseline CD4 count of ≥ 50 cells/mm 3 achieved undetectable viral load, this fell to < 20% for those with lower CD4 counts
  • 55% of participants had at least a 1 log decrease and 48% had at least a 2 log decrease in HIV RNA; the average reduction from baseline was 1.6 log
  • The overall average CD4 cell gain was 48 cells/mm 3, but this differed according to baseline level: people who started with at least 50 cells/mm 3 saw a mean gain of about 75 cells/mm 3, while those with lower baseline levels gained an average of 9 cells/mm 3

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