OpenLB
Open Library of Bioscience
Advanced Search
Current opinion in HIV and AIDS
Jan 01, 2025;20 (1): 4-10.

Long-acting antiretroviral therapy in the context of viral suppression.

Kyle Ring, Chloe Orkin
Author Information
  1. Kyle Ring: Blizard Institute, Centre for Immunology and Infectious Disease: Queen Mary University of London.
  2. Chloe Orkin: Blizard Institute, Centre for Immunology and Infectious Disease: Queen Mary University of London.
PMID: 39633535 DOI: 10.1097/COH.0000000000000897

Abstract

PURPOSE OF REVIEW: Long-acting antiretroviral therapy (ART), such as with cabotegravir and rilpivirine, is a new and exciting paradigm shift that could change the face of HIV treatment if it were universally available to all who want it. In countries where there is access, uptake has been slow - partly because of capacity issues and partly because of hesitancy around remaining clinical questions. We summarized clinical trial data and emerging real-world evidence to shed light on these questions.
RECENT FINDINGS: Phase 2b/3/3b clinical trials have shown CAB+RPV injections to be both well tolerated and efficacious. Real-world cohort (RWC) studies with larger numbers of people demonstrate high levels of adherence and persistence, and low rates of virological failure in clinical practice.
SUMMARY: Although the risk of virological failure in the context of CAB+RPV is low, it remains a pertinent issue because of the high risk of developing two-class resistance. The use of multiple definitions of virological failure in RWC studies currently makes understanding the available evidence difficult and could have deleterious effects on clinical decision-making. Longer term real-world evidence in diverse populations is needed to better understand the durability of CAB+RPV and its suitability in different contexts.

References

  1. Viswanathan S, Detels R, Mehta SH, et al. Level of adherence and HIV RNA suppression in the current era of highly active antiretroviral therapy (HAART). AIDS Behav 2015; 19:601���611.
  2. Lazarus JV, Safreed-Harmon K, Barton SE, et al. Beyond viral suppression of HIV - the new quality of life frontier. BMC Med 2016; 14:94.
  3. The urgency of now: AIDS at a crossroads [Internet]. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS; 2024 [cited 14 July 2024]. Available at: https://www.unaids.org/sites/default/files/media_asset/2024-unaids-global-aids-update_en.pdf . [Accessed 7 August 2024].
  4. Kall M, Marcellin F, Harding R, et al. Patient-reported outcomes to enhance person-centred HIV care. Lancet HIV 2020; 7:e59���68.
  5. Aghaizu A, Martin V, Kelly C, et al. Positive voices: The National Survey of People Living with HIV. Findings from 2022. Report summarising data from 2022 and measuring change since 2017 [Internet]. UK Health Security Agency; 2023 December [cited 20 July 2024]. Available at: https://www.gov.uk/government/publications/hiv-positive-voices-survey/positive-voices-2022-survey-report . [Accessed 7 August 2024].
  6. Positive Perspectives Study, Wave 2 Results Report [Internet]. ViiV Healthcare; 2021 Jun [cited 20 July 2024]. Report No.: NP-GBL-HVU-OGM-200001. Available at: https://viivhealthcare.com/content/dam/cf-viiv/viivhealthcare/en_GB/files/211203-updated-pp2-report-v9.0.pdf
  7. Kremer IEH, Beaudart C, Simons J, et al. Preferences of people living with HIV for injectable and oral antiretroviral treatment in the Netherlands: a discrete choice experiment. AIDS Care 2024; 36:536���545.
  8. Graham SM, Barthold D, Hauber B, et al. U.S. patient preferences for long-acting HIV treatment: a discrete choice experiment. J Int AIDS Soc 2023; 26 (S2):e26099.
  9. European Medicines Agency. Vocabria summary of product characteristics [Internet]. [cited 26 February 2024]. Available at: https://www.ema.europa.eu/en/documents/product-information/vocabria-epar-product-information_en.pdf . [Accessed 7 August 2024].
  10. Ambrosioni J, Levi L, Alagaratnam J, et al. Major revision version 12 0 of the European AIDS Clinical Society guidelines 2023. HIV Med 2023; 24:1126���1136.
  11. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV [Internet]. Department of Health and Human Services; 2024 [cited 12 September 2024]. Available at: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv . [Accessed 7 August 2024].
  12. Gandhi RT, Bedimo R, Hoy JF, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2022 recommendations of the International Antiviral Society-USA Panel. JAMA 2023; 329:63.
  13. Waters L, Winston A, Reeves I, et al. BHIVA guidelines on antiretroviral treatment for adults living with HIV-1. HIV Med 2022; 23 Suppl:3���115.
  14. Smith GHR, Henry WK, Podzamczer D, et al. Efficacy, safety, and durability of long-acting cabotegravir and rilpivirine in adults with human immunodeficiency virus type 1 infection: 5-year results from the LATTE-2 Study. Open Forum Infect Dis 2021; 8:ofab439.
  15. Orkin C, Arasteh K, G��rgolas Hern��ndez-Mora M, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection. N Engl J Med 2020; 382:1124���1135.
  16. Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med 2020; 382:1112���1123.
  17. Orkin C, Oka S, Philibert P, et al. Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV 2021; 8:e185���e196.
  18. Swindells S, Lutz T, Van Zyl L, et al. Week 96 extension results of a Phase 3 study evaluating long-acting cabotegravir with rilpivirine for HIV-1 treatment. AIDS 2022; 36:185���194.
  19. Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2���months in adults with HIV-1 infection (ATLAS-2���M), 48-week results: a randomised, multicentre, open-label, phase 3b, noninferiority study. Lancet 2020; 396:1994���2005.
  20. Jaeger H, Overton ET, Richmond G, et al. Long-acting cabotegravir and rilpivirine dosed every 2���months in adults with HIV-1 infection (ATLAS-2���M), 96-week results: a randomised, multicentre, open-label, phase 3b, noninferiority study. Lancet HIV 2021; 8:e679���e689.
  21. Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with human immunodeficiency virus 1 type 1 infection: 152-week results from ATLAS-2M, a randomized, open-label, phase 3b, noninferiority study. Clin Infect Dis 2023; 76:1646���1654.
  22. Orkin C, Schapiro JM, Perno CF, et al. Expanded multivariable models to assist patient selection for long-acting cabotegravir + rilpivirine treatment: clinical utility of a combination of patient, drug concentration, and viral factors associated with virologic failure. Clin Infect Dis 2023; 77:1423���1431.
  23. Orkin C, Bernal Morell E, Tan DHS, et al. Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study. Lancet HIV 2021; 8:e668���e678.
  24. Ramgopal MN, Castagna A, Cazanave C, et al. Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV, 12-month results (SOLAR): a randomised, open-label, phase 3b, noninferiority trial. Lancet HIV 2023; 10:e566���e577.
  25. Global HIV Statistics [Internet]. UNAIDS; 2024 [cited 14 July 2024]. Available at: https://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf . [Accessed 7 August 2024].
  26. Elias A, Smuk M, Whelan I, et al. Inclusion of women, racially minoritised people and older adults in real-world studies evaluating long-acting injectable cabotegravir and rilpivirine: a scoping review. Poster presented at: BHIVA Spring Conference 2024; 2024; Birmingham, UK. Available at: https://onlinelibrary.wiley.com/toc/14681293/2024/25/S1 . [Accessed 7 August 2024].
  27. Kityo C, Mambule IK, Musaazi J, et al. Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): week 48 results from a randomised, multicentre, open-label, noninferiority trial. Lancet Infect Dis 2024; S1473309924002895.
  28. Garris CP, Czarnogorski M, Dalessandro M, et al. Perspectives of people living with HIV-1 on implementation of long-acting cabotegravir plus rilpivirine in US healthcare settings: results from the CUSTOMIZE hybrid III implementation-effectiveness study. J Int AIDS Soc 2022; 25:e26006.
  29. De Wit S, Rami A, Bonnet F, et al. 1584. CARISEL A Hybrid III Implementation Effectiveness Study of implementation of Cabotegravir plus Rilpivirine Long Acting (CAB+RPV LA) in EU Healthcare Settings Key Clinical and Implementation Outcomes by Implementation Arm. Open Forum Infect Dis 2022; 9: (Suppl 2): ofac492.107.
  30. Orkin C, Hayes R, Haviland J, et al. Perspectives of people with HIV on implementing long acting cabotegravir plus rilpivirine in clinics and community settings in the UK: results from the anti-sexist, anti-racist, anti-ageist ILANA study. Clin Infect Dis 2024; ciae523Available from: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciae523/7846271 . [Accessed 6 November 2024]. [DOI: 10.1093/cid/ciae523/7846271]
  31. Sension M, Hsu RK, Fusco JS, et al. 1608. Real-world effectiveness of long-acting cabotegravir + rilpivirine in virologically suppressed treatment-experienced individuals: two years of data from the OPERA�� Cohort. Open Forum Infect Dis 2023; 10: (Suppl 2): ofad500.1443.
  32. Deschanvres C, Allavena C, Palich R, et al. Cabotegravir-rilpivirine long acting: data in real life setting in a French Cohort. In Warsaw, Poland; 2023. Available at: https://www.natap.org/2023/EACS/EACS_59.htm . [Accessed 7 August 2024].
  33. Ring K, Elias A, Smuk M, et al. Definitions of virological failure in real-world cabotegravir + rilpivirine cohorts are inconsistent (abstract P001). In Birmingham; 2024 [cited 20 May 2024]. Available at: https://doi.org/10.1111/hiv.13628 . [Accessed 7 August 2024].
  34. Pozniak A, Sridhar G, Assoumou L, et al. Real-world utilization and effectiveness of long-acting cabotegravir + rilpivirine in virologically suppressed treatment experienced individuals in Europe: data from COMBINE-2 Cohort Study. In Munich; 2024. Available at: https://www.natap.org/2024/IAS/IAS_42.htm . [Accessed 7 August 2024].
  35. Maguire C, Farmer E, Huesgen E, et al. Real-world virologic outcomes of cabotegravir/rilpivirine in patients with elevated body mass index. In Denver, CO; 2024. Available at: https://www.croiconference.org/abstract/real-world-virologic-outcomes-of-cabotegravir-rilpivirine-in-patients-with-elevated-body-mass-index/ . [Accessed 7 August 2024].
  36. Eron J, Sarkar S, Frick A, Radtchenko J, et al. Real-world utilization of cabotegravir + rilpivirine in the US: data from Trio Health Cohort. In Denver, CO; 2024. Available at: https://www.croiconference.org/wp-content/uploads/sites/2/posters/2024/625.pdf . [Accessed 7 August 2024].
  37. Sinclair GI, Sension M, Dretler A, et al. 1607. Clinical outcomes at month 6 after initiation of cabotegravir and rilpivirine long-acting (CAB + RPV LA) in an observational real-world study (BEYOND). Open Forum Infect Dis 2023; 10: (Suppl 2): ofad500.1442.
  38. Nielsen N, Taranto B, Sobhanie MM, et al. 1594. Outcomes in patients receiving long-acting cabotegravir-rilpivirine in a community, infusion center-based administration model in Columbus, Ohio. Open Forum Infect Dis 2023; 10: (Suppl 2): ofad500.1429.
  39. Ferr�� V, Serris A, Le Hingrat Q, et al. Real-world data on commercial long-acting intramuscular maintenance therapy with cabotegravir and rilpivirine mirror phase 3 results: findings from a University Hospital in Paris, France (EACS2023: 878). In Warsaw, Poland; 2023. Available at: https://onlinelibrary.wiley.com/doi/10.1111/hiv.13572 . [Accessed 7 August 2024].
  40. Shankaran S, Hernandez-Guarin L, Jhobalia N, et al. Virologic failure with cabotegravir-rilpivirine injections: a single-site experience. In Denver, CO; 2024 [cited 6 August 2024]. Available at: https://www.croiconference.org/wp-content/uploads/sites/2/posters/2024/686.pdf . [Accessed 7 August 2024].
  41. Rubenstein E, Diemer M, Goldwirt L, et al. Low cabotegravir trough concentrations without oral lead-in in patients with HIV-1 switching to long-acting cabotegravir and rilpivirine. AIDS 2024; 38:1267���1269.
  42. John M, Williams L, Nolan G, et al. Real-world use of long-acting cabotegravir and rilpivirine: 12-month results of the inJectable Antiretroviral therapy feasiBility Study (JABS). HIV Medicine [Internet] 2024; 25:935���945.
  43. Iannone V, Lombardi F, Salvo PF, et al. CAB + RPV long-acting antiretroviral therapy: real world data from an Italian single center in Roma (EACS2023: 563). In Warsaw, Poland; 2023. Available at: https://onlinelibrary.wiley.com/doi/10.1111/hiv.13572 . [Accessed 7 August 2024].
  44. Keiju K, Yu K, Ethico-Tokushi S, et al. O26-2 On the change from oral to long-acting injectable antiretroviral therapy. In Kyoto, Japan; 2023.
  45. Roberts J, Paul L, Richardson C, Jaquiss J, et al. A shot in the dark: a review one year on after initiation of injectable HIV treatment in a UK HIV outpatient clinic (EACS2023: 977). Warsaw, Poland; 2023. Available at: https://onlinelibrary.wiley.com/doi/10.1111/hiv.13572 . [Accessed 7 August 2024].
  46. Montalvo S, Sherman E, Eckardt PA, et al. 1591. Real-world experiences and outcomes implementing long-acting cabotegravir/rilpivirine at a Ryan White HIV/AIDS Program (RWHAP)-funded clinic in South Florida. Open Forum Infect Dis 2023; 10: (Suppl 2): ofad500.1426.
  47. Masich AM, Gomes D, Higginson RT, et al. HIV virologic response and baseline genotypic resistance in a long-acting cabotegravir/rilpivirine initiation program. AIDS 2023; 37:1641���1642.
  48. Talarico CL, Wu S, Upadhyay OR, et al. HIV-1 RNA blips and low-level replication during phase III/IIIb cabotegravir + rilpivirine long-acting studies are similar to oral 3-drug therapy and not associated with week 48 virologic outcome. Open Forum Infect Dis 2020; 7: (Suppl 1): S540���S541.
  49. Latham C, Urbaityte R, Sutton K, et al. HIV-1 RNA blips and low-level viral replication: SOLAR (CAB + RPV LA vs. BIC/FTC/TAF). In Denver, CO; 2024. Available at: https://medinfo.gsk.com/5f95dbd7-245e-4e65-9f36-1a99e28e5bba/60873bf9-6441-45c4-a10d-acc2ade02637/60873bf9-6441-45c4-a10d-acc2ade02637_viewable_rendition__v.pdf . [Accessed 7 August 2024].
  50. Hill L, Kenney S, Patel N, et al. Predictors of postswitch viremia in people with HIV on injectable cabotegravir/rilpivirine. JAIDS J Acquir Immune Defic Syndr 2024; 95:90���96.
  51. Bertoni C, Svicher V, Bagaglio S, et al. Single center study on participants living with HIV with isolated anticore antibody (anti-HBc) switching to long acting cabotegravir-rilpivirine therapy: results from the SCohoLART study. Warsaw, Poland; 2023. Available at: https://onlinelibrary.wiley.com/doi/10.1111/hiv.13572 . [Accessed 7 August 2024].
  52. Delany-Moretlwe S, Voldal E, Said F. Initial evaluation of injectable cabotegravir (CAB-LA) safety during pregnancy in the HPTN 084 open-label extension. AIDS 2024, the 25th International AIDS Conference, Munich, Germany 22���26 July 2024 (Abstract SY25).
  53. Patel P, Ford SL, Baker M, et al. Pregnancy outcomes and pharmacokinetics in pregnant women living with HIV exposed to long-acting cabotegravir and rilpivirine in clinical trials. HIV Med 2023; 24:568���579.
  54. Vannappagari V, Albano J, Thorne C, et al. Pregnancy and neonatal outcomes following prenatal exposure to cabotegravir (CAB): data from the Antiretroviral Pregnancy Registry (APR) and European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC). Charleston, SC; 2023.

MeSH Term

Humans
HIV Infections
Anti-HIV Agents
Rilpivirine
Antiretroviral Therapy, Highly Active
Viral Load
Pyridones
Diketopiperazines

Chemicals

Anti-HIV Agents
Rilpivirine
cabotegravir
Pyridones
Diketopiperazines
Journal Article Review

Word Cloud

Created with Highcharts 10.0.0clinicalevidenceCAB+RPVvirologicalfailureLong-actingantiretroviraltherapyavailablepartlyquestionsreal-worldRWCstudieshighlowriskcontextPURPOSEOFREVIEW:ARTcabotegravirrilpivirinenewexcitingparadigmshiftchangefaceHIVtreatmentuniversallywantcountriesaccessuptakeslow-capacityissueshesitancyaroundremainingsummarizedtrialdataemergingshedlightRECENTFINDINGS:Phase2b/3/3btrialsshowninjectionswelltoleratedefficaciousReal-worldcohortlargernumberspeopledemonstratelevelsadherencepersistenceratespracticeSUMMARY:Althoughremainspertinentissuedevelopingtwo-classresistanceusemultipledefinitionscurrentlymakesunderstandingdifficultdeleteriouseffectsdecision-makingLongertermdiversepopulationsneededbetterunderstanddurabilitysuitabilitydifferentcontextsviralsuppression

Similar Articles

Cited By