Fostemsavir lowers HIV-1 RNA levels

  • Kozal M & al.
  • N Engl J Med
  • 26 Mar 2020

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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Takeaway

  • In patients with multidrug-resistant human immunodeficiency virus-1 (HIV-1) infection with limited therapy options, fostemsavir had significantly better efficacy than placebo in reducing the mean HIV-1 ribonucleic acid (RNA) level during the first 8 day.
  • Efficacy was sustained through 48 weeks.

Why this matters

  • Findings support the future development of fostemsavir as a therapeutic option for patients with multidrug-resistant HIV-1 infection and few remaining options for active therapy.

Study design

  • In this ongoing phase 3 BRIGHTE trial, 371 patients with multidrug-resistant HIV-1 were divided into 2 cohorts
    • First cohort (randomised): 272 patients were randomly assigned (3:1) to receive either fostemsavir or placebo for 8 days, then received open-label fostemsavir.
    • Second cohort (nonrandomised): 99 patients received open-label fostemsavir plus optimised background therapy on day 1.
  • Primary outcome: mean change in the HIV-1 RNA level from day 1 to day 8 in the randomised cohort.
  • Funding: Bristol-Myers Squibb and GSK/ViiV Healthcare.

Key results

  • At day 8, the mean reduction in the HIV-1 RNA level was higher in the fostemsavir vs placebo group (between-group difference, −0.63 log10 copies/mL in the fostemsavir group; 95% CI, −0.81 to −0.44; P<.001>
  • At 48 weeks, virologic response rates (HIV-1 RNA level,
  • Overall, discontinuation of fostemsavir because of adverse events was reported in 27 (7%) patients.
  • In the randomised cohort, glycoprotein 120 substitutions were reported in 20 (43%) of 47 patients with virologic failure.

Limitations

  • Study did not include comparator group beyond the analysis of the primary endpoint.
  • Confounder of highly individualized optimised background therapy.