Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection

N Engl J Med. 2020 Mar 19;382(12):1124-1135. doi: 10.1056/NEJMoa1909512. Epub 2020 Mar 4.

Abstract

Background: Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection.

Methods: We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm).

Results: At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, -0.4 percentage points; 95% confidence interval [CI], -2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, -3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, -10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48.

Conclusions: Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir-abacavir-lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.).

Publication types

  • Clinical Trial, Phase III
  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / blood
  • Anti-Retroviral Agents / therapeutic use
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral / genetics
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • Humans
  • Induction Chemotherapy
  • Injections, Intramuscular
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Mutation
  • Patient Reported Outcome Measures
  • Pyridones / administration & dosage*
  • Pyridones / adverse effects
  • Pyridones / blood
  • RNA, Viral / blood
  • Rilpivirine / administration & dosage*
  • Rilpivirine / adverse effects
  • Rilpivirine / blood
  • Viral Load

Substances

  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • Pyridones
  • RNA, Viral
  • Rilpivirine
  • cabotegravir

Associated data

  • ClinicalTrials.gov/NCT02938520