Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression

N Engl J Med. 2020 Mar 19;382(12):1112-1123. doi: 10.1056/NEJMoa1904398. Epub 2020 Mar 4.


Background: Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence.

Methods: In this phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy, we randomly assigned participants (1:1) to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and long-acting rilpivirine, a nonnucleoside reverse-transcriptase inhibitor. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, determined with the use of the Food and Drug Administration snapshot algorithm.

Results: Treatment was initiated in 308 participants per group. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 5 participants (1.6%) receiving long-acting therapy and in 3 (1.0%) receiving oral therapy (adjusted difference, 0.6 percentage points; 95% confidence interval [CI], -1.2 to 2.5), a result that met the criterion for noninferiority for the primary end point (noninferiority margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy (adjusted difference, -3.0 percentage points; 95% CI, -6.7 to 0.7), a result that met the criterion for noninferiority for this end point (noninferiority margin, -10 percentage points). Virologic failure was confirmed in 3 participants who received long-acting therapy and 4 participants who received oral therapy. Adverse events were more common in the long-acting-therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy and was mild or moderate in most cases; 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group.

Conclusions: Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal. (Funded by ViiV Healthcare and Janssen; ATLAS ClinicalTrials.gov number, NCT02951052.).

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
  • Injections, Intramuscular / adverse effects
  • 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


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

Associated data

  • ClinicalTrials.gov/NCT02951052