The future of long-acting cabotegravir plus rilpivirine therapy: deeds and misconceptions

Int J Antimicrob Agents. 2022 Sep;60(3):106627. doi: 10.1016/j.ijantimicag.2022.106627. Epub 2022 Jun 24.

Abstract

HIV infection is currently managed as a chronic disease because of improvements in antiretroviral therapy (ART). Switching to a new regimen is a natural event during long-term therapy to avoid problems related to toxicity, adherence, failure, and potential selection of drug resistance. The development of co-formulations of multiple agents in one pill, and novel drug classes and drugs with a high genetic barrier to resistance have been important in this context. The approval of the long-acting, once-monthly or bimonthly injectable combination of the second-generation strand transfer integrase inhibitor (InSTI), cabotegravir (CAB) together with the non-nucleoside reverse transcriptase inhibitor (NNRTI), rilpivirine (RPV) represents the most recent achievement in the search for potent and convenient ART. Several pivotal trials (such as LATTE-2, ATLAS, FLAIR, and ATLAS-2M) showed the high efficacy and safety of this long-acting formulation used as an induction-maintenance strategy. Few confirmed virological failures (CVF) have been observed. The combination of at least two of the following baseline factors, HIV-1 subtype A6/A1, a body mass index (BMI) ≥30 kg/m2, and RPV resistance-associated mutations, was associated with an increased risk of CVF at week 48. The data indicate that this long-acting therapeutic strategy is attractive and potent; therefore, defining the most appropriate patient for this treatment and how to handle practical issues is warranted.

Keywords: HIV; antiretroviral therapy; cabotegravir; integrase inhibitors; long-acting; rilpivirine.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents* / adverse effects
  • Diketopiperazines
  • HIV Infections* / drug therapy
  • HIV-1*
  • Humans
  • Pyridones / therapeutic use
  • Rilpivirine / therapeutic use

Substances

  • Anti-HIV Agents
  • Diketopiperazines
  • Pyridones
  • Rilpivirine
  • cabotegravir