IAS 2019 — New drugs in a dual HIV treatment regimen show promise

  • Laura Vargas-Parada, Ph.D.
  • Conference Reports
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  • Dual therapy with MK-8591 in combination with doravirine (DOR) was well-tolerated while participants achieved and maintained viral suppression among all treatment groups in study assessing efficacy and safety data. 

Why this matters 

  • MK-8591 (islatravir) is the first nucleoside reverse transcriptase translocation inhibitor in development for treatment of HIV-1 infection. 
  • DOR is a recently approved non-nucleoside reverse transcriptase inhibitor. 

Study design 

  • Phase 2B, double-blind, comparator-controlled, dose-ranging trial to evaluate efficacy and safety of MK-8591 with DOR. 
  • 121 patients (mean age, 31 years; 92.6% male, 76.0% white, 22% HIV-1 RNA >100,000 copies/mL) were randomly allocated to 1 of 4 study arms. 
    • First 24 weeks, equal number of patients received 1 of 3 doses of MK-8591 (0.25, 0.75, or 2.25 mg) plus DOR (100 mg) and 3TC (lamivudine; 300 mg) or DOR/3TC/TDF (tenofovir disoproxil) once daily with placebo. 
    • After 24 weeks, those on MK-8591 who achieved HIV-1 RNA
  • Efficacy endpoints included overall proportion of patients at week 48 with HIV-1 RNA
  • Safety was assessed by adverse event reporting.

Key results  

  • Proportion of patients achieving HIV-1 RNA
  • 0.25 mg, 89.7%; 
  • 0.75 mg, 90.0%; 
  • 2.25 mg, 77.4%; and 
  • With DOR/3TC/TDF, 83.9%. 
  • Mean change in CD4+ T-cell count was similar for all groups. 
  • No patient had HIV-1 RNA >200 copies/mL or documented resistance to study drugs. 
  • Adverse events reported: 
    • MK-8591, any dose (combined 7.8%).
    • DOR/3TC/TDF (19.4%).
  • Limitations

    • Conference presentation reported without peer review. 

    Expert comment 

    • “These are promising data that encouraged the company to move to a phase 3 trial to see how these results can confirm in a larger study site and also to assess this dual combination for therapy in the future providing novel options for people,” said Jean-Michel Molina, the study’s lead investigator from Paris Diderot University and Saint-Louis Hospital, during a press conference.