cabotegravir with rilpivirine for treating HIV-1 (HIV)

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Rilpivirine, a non-nucleoside reverse trancriptase inhibitor (NNRTI), has been shown to have efficacy in HIV treatment when delivered as injectable anti-retroviral maintenance therapy in combination with cabotegravir in persons living with HIV (PLWH) who have not previously experienced virologic failure (1):

  • despite being safe, well-tolerated, and acceptable for PrEP in key populations, long-acting rilpivirine for PrEP has not moved forward into phase 3 studies due to storage and transportation limitations (cold chain required) and a low barrier to resistance

Cabotegravir (formerly GSK1265744) is an integrase strand transfer inhibitor (INSTI) with potent antiviral activity

  • a chemical congener of dolutegravir, it has a high barrier to resistance and retains activity in the setting of common INSTI mutations
  • is amenable to formulation as a long-acting injectable suspension
    • the injectable suspension is effectively composed of pure active drug in crystalline form, meaning near complete drug loading per unit volume (200 mg/ml) and a small injection load.

NICE state that:

Cabotegravir with rilpivirine is recommended, within its marketing authorisation, as an option for treating HIV-1 infection in adults:

  • with virological suppression (HIV-1 RNA fewer than 50 copies/ml) on a stable antiretroviral regimen and

  • without any evidence of viral resistance to, and no previous virological failure with, any non-nucleoside reverse transcriptase inhibitors or integrase inhibitors

Rizzardini et al compared long-acting regimen of cabotegravir and rilpivirine verses current antiretroviral regimen in participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1)

  • participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV)
  • combined analysis demonstrated that monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression


  • NICE note that current treatment for HIV-1 is antiretroviral regimens taken as tablets (orally) each day. The aim is to keep the number of virus particles in the blood (the viral load) so low that it cannot be detected, so that the virus cannot be transmitted between people. Cabotegravir with rilpivirine is the first long-acting antiretroviral injection available for HIV-1
    • clinical trial results show that cabotegravir with rilpivirine is as effective as oral antiretrovirals at keeping the viral load lower than 50 copies/ml of blood


  • Clement ME, Kofron R, Landovitz RJ. Long-acting injectable cabotegravir for the prevention of HIV infection. Curr Opin HIV AIDS. 2020;15(1):19-26. doi:10.1097/COH.0000000000000597
  • Rizzardini G, Overton ET, Orkin C, et al. Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials. Journal of Acquired Immune Deficiency Syndromes (1999). 2020 Dec;85(4):498-506. DOI: 10.1097/qai.0000000000002466. PMID: 33136751; PMCID: PMC7592884.
  • NICE (January 2022). Cabotegravir with rilpivirine for treating HIV-1

Last edited 01/2022 and last reviewed 01/2022