Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential

References

• Joint United Nations Programme on HIV & AIDS. UNAIDS Data 2018. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS (UNAIDS); 2018 Available from: https://www.aidsdatahub.org/sites/default/files/publication/UNAIDS_Data_2018.pdf
   Google Scholar
• Joint United Nations Programme on HIV/AIDS (UNAIDS). 90-90-90 an Ambitious Treatment Target to Help End the AIDS Epidemic. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS (UNAIDS); Vol. 1.; 2014.
   Google Scholar
• Harris TG, Rabkin M, El-Sadr WM. Achieving the fourth 90: healthy aging for people living with HIV. AIDS. 2018;32(12):1563–1569. doi:10.1097/QAD.000000000000187029762172
   PubMed Web of Science ®Google Scholar
• Lazarus JV, Safreed-Harmon K, Barton SE, et al. Beyond viral suppression of HIV – the new quality of life frontier. BMC Med. 2016;14(1):94. doi:10.1186/s12916-016-0640-427334606
   PubMed Web of Science ®Google Scholar
• Whitfield T, Torkington A, van Halsema C. Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date. HIV/AIDS - Res Palliat Care. 2016;8:157–164. doi:10.2147/HIV.S97920
   Google Scholar
• Ferretti F, Boffito M. Rilpivirine long-acting for the prevention and treatment of HIV infection. Curr Opin HIV AIDS. 2018;13(4):300–307. doi:10.1097/COH.000000000000047429794818
   PubMed Web of Science ®Google Scholar
• ViiV Healthcare. GSK1265744 (Cabotegravir, CAB) for named patient/compassionate use in HIV. ClinicalTrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT03462810. Published 2018 Accessed 430, 2019.
   Google Scholar
• Spreen W, Min S, Ford SL, et al. Pharmacokinetics, safety, and monotherapy antiviral activity of GSK1265744, an HIV integrase strand transfer inhibitor. HIV Clin Trials. 2013;14(5):192–203. doi:10.1310/hct1405-19224144896
   PubMed Web of Science ®Google Scholar
• Spreen W, Ford SL, Chen S, et al. GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects. J Acquir Immune Defic Syndr. 2014;67(5):481–486. doi:10.1097/QAI.000000000000030125140909
   PubMed Web of Science ®Google Scholar
• Committee for Medicinal Products for Human Use. Edurant - Rilpivirine. Amsterdam, the Netherlands: European Medicines Agency; 2011 Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/edurant. Accessed 122, 2019.
   Google Scholar
• Food and Drug Administration. Rilpivirine. Maryland, USA: AIDSinfo; 2011 Available from: https://aidsinfo.nih.gov/drugs/426/rilpivirine/19/professional. Accessed April 30, 2019.
   Google Scholar
• Molina J-M, Cahn P, Grinsztejn B, et al. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet (London, England). 2011;378(9787):238–246. doi:10.1016/S0140-6736(11)60936-7
   PubMed Web of Science ®Google Scholar
• Cohen CJ, Andrade-Villanueva J, Clotet B, et al. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011;378(9787):229–237. doi:10.1016/S0140-6736(11)60983-521763935
   PubMed Web of Science ®Google Scholar
• Healthcare V. Juluca 50 mg/25 mg film-coated tablets. electronic Medicines Compendium; 2019. Available from: https://www.medicines.org.uk/emc/product/9246/smpc. Accessed 5 2, 2019.
   Google Scholar
• Gilead Sciences. Odefsey 200 mg/25 mg/25 mg film-coated tablets. electronic Medicines Compendium; 2018. Available from: https://www.medicines.org.uk/emc/product/7262/smpc.Accessed 52, 2019.
   Google Scholar
• Gilead Sciences. Eviplera 200 Mg/25 Mg/245 Mg Film Coated Tablets. Surrey, UK: Electronic Medicines Compendium; 2018 Available from: https://www.medicines.org.uk/emc/product/2764/smpc. Accessed May 2, 2019.
   Google Scholar
• Janssen Pharmaceuticals. Pre-Approval Access to Rilpivirine Long Acting (RPV LA) Injectable Suspension for the Treatment of a Participant with Human Immunodeficiency Virus (HIV)-1 Infection. Maryland, USA: AIDSinfo; 2019 Available from: https://aidsinfo.nih.gov/clinical-trials/details/NCT03847376. Accessed 430, 2019.
   Google Scholar
• Jackson AGA, Else LJ, Mesquita PMM, et al. A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis. Clin Pharmacol Ther. 2014;96(3):314–323. doi:10.1038/clpt.2014.11824862215
   PubMed Web of Science ®Google Scholar
• Verloes R, Deleu S, Niemeijer N, Crauwels H, Meyvisch P, Williams P. Safety, tolerability and pharmacokinetics of rilpivirine following administration of a long-acting formulation in healthy volunteers. HIV Med. 2015;16(8):477–484. doi:10.1111/hiv.1224725988676
   PubMed Web of Science ®Google Scholar
• McGowan I, Dezzutti CS, Siegel A, et al. Long-acting rilpivirine as potential pre-exposure prophylaxis for HIV-1 prevention (the MWRI-01 study): an open-label, phase 1, compartmental, pharmacokinetic and pharmacodynamic assessment. Lancet HIV. 2016;3(12): e569-e578. doi:10.1016/S2352-3018(16)30113-8
   Web of Science ®Google Scholar
• University of Liverpool. HIV drug interactions. Available from: https://www.hiv-druginteractions.org/checker. Published 2019 Accessed 430, 2019.
   Google Scholar
• Janssen Pharmaceuticals. Edurant 25 Mg Tablets - Summary of Product Characteristics. Surrey, UK: Electronic Medicines Compendium; 2018. Available from: https://www.medicines.org.uk/emc/product/4968/smpc#companyDetails. AccessedJanuary 22, 2019.
   Google Scholar
• Ford SL, Gould E, Chen S, et al. Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and GSK1265744. Antimicrob Agents Chemother. 2013;57(11):5472–5477. doi:10.1128/AAC.01235-1323979733
   PubMed Web of Science ®Google Scholar
• Margolis DA, Brinson CC, Smith GHR, et al. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial. Lancet Infect Dis. 2015;15(10):1145–1155. doi:10.1016/S1473-3099(15)00152-826201299
   PubMed Web of Science ®Google Scholar
• Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet. 2017;390(10101):1499–1510. doi:10.1016/S0140-6736(17)31917-728750935
   PubMed Web of Science ®Google Scholar
• Margolis D, Gonzalez-Garcia J, Stellbrink H-J, et al. Safety, efficacy and durability of long-acting cabotegravir and rilpivirine as two-drug IM maintenance therapy for HIV-1 infection: LATTE-2 week 160 results In: HIV Glasgow. Glasgow; 2018:Poster 118.
   Google Scholar
• Stanford University. HIV drug resistance database. 2019. Available from: https://hivdb.stanford.edu/. Accessed 4 30, 2019.
   Google Scholar
• Orkin C, Arastéh K, Hernández-Mora Gorgolas M, et al. Long acting cabortegravir + rilpivirine for HIV maintenance: FLAIR week 48 results. Conference on Retroviruses and Opportunistic Infections; 2019:Abstract 140 Seattle.
   Google Scholar
• Swindells S, J-F A-V, Richmond GJ, et al. Long-acting cabotegravir + rilpivirine as maintenance therapy: atlas week 48 resultS. Conference on Retroviruses and Opportunistic Infections; 2019:Abstract 139 Seattle.
   Google Scholar
• ViiV Healthcare. Study evaluating the efficacy, safety, and tolerability of switching to long-acting cabotegravir plus long-acting rilpivirine from current antiretroviral regimen in virologically suppressed HIV-1-infected adults. ClinicalTrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT02951052. Published 2018 Accessed 131, 2019.
   Google Scholar
• Allavena C, Rodallec A, Leplat A, et al. Interest of proviral HIV-1 DNA genotypic resistance testing in virologically suppressed patients candidate for maintenance therapy. J Virol Methods. 2018;251:106–110. doi:10.1016/j.jviromet.2017.10.01629042218
   PubMed Web of Science ®Google Scholar
• Armenia D, Zaccarelli M, Borghi V, et al. Resistance detected in PBMCs predicts virological rebound in HIV-1 suppressed patients switching treatment. J Clin Virol. 2018;104:61–64. doi:10.1016/j.jcv.2018.04.00129738896
   PubMed Web of Science ®Google Scholar
• Kerrigan D, Mantsios A, Gorgolas M, et al. Experiences with long acting injectable ART: A qualitative study among PLHIV participating in a Phase II study of cabotegravir + rilpivirine (LATTE-2) in the United States and Spain. PLoS One. 2018;13(1):e0190487. doi:10.1371/journal.pone.019048729304154
   PubMed Web of Science ®Google Scholar
• Woodcock A, Psychol C, Bradley C. Validation of the revised 10-item HIV treatment satisfaction questionnaire status version and new change version. Value Heal. 2006;9(5):320–333. doi:10.1111/j.1524-4733.2006.00121.x
   PubMed Web of Science ®Google Scholar
• Woodcock A, Bradley C. Validation of the HIV treatment satisfaction questionnaire (HIVTSQ). Qual Life Res. 2001;10(6):517–531. AccessedApril 22, 2019. doi:10.1023/A:101305090463511789552
   PubMed Web of Science ®Google Scholar
• Romaine J, Murray M, Bradley C. Psychometric evaluation of the revised hiv treatment satisfaction questionnaire (Hivtsq). Value Heal. 2016;19(7):A420. doi:10.1016/j.jval.2016.09.426
   Web of Science ®Google Scholar
• Landovitz RJ, Li S, Grinsztejn B, et al. Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial. PLoS Med. 2018; 15(11):e1002690 Newell M-L, ed. doi:10.1371/journal.pmed.100259330408115
   PubMed Web of Science ®Google Scholar
• Murray MI, Markowitz M, Frank I, et al. Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: patient perspectives from the ECLAIR trial. HIV Clin Trials. 2018;19(4):129–138. doi:10.1080/15284336.2018.151134630445896
   PubMed Web of Science ®Google Scholar
• Cuzin L, Pugliese P, Katlama C, et al. Integrase strand transfer inhibitors and neuropsychiatric adverse events in a large prospective cohort. J Antimicrob Chemother. 2019;74(3):754–760. doi:10.1093/jac/dky49730534993
   PubMed Web of Science ®Google Scholar
• MGJ DB, GEL VDB, van Holten N, et al. Intolerance of dolutegravir-containing combination antiretroviral therapy regimens in real-life clinical practice. AIDS. 2016;30(18):2831–2834. doi:10.1097/QAD.000000000000127927824625
   PubMed Web of Science ®Google Scholar
• Fettiplace A, Stainsby C, Winston A, et al. Psychiatric symptoms in patients receiving dolutegravir. JAIDS J Acquir Immune Defic Syndr. 2017;74(4):423–431. doi:10.1097/QAI.000000000000126927984559
   PubMed Web of Science ®Google Scholar
• Hoffmann C, Welz T, Sabranski M, et al. Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients. HIV Med. 2017;18(1):56–63. doi:10.1111/hiv.1246827860104
   PubMed Web of Science ®Google Scholar
• Peñafiel J, de Lazzari E, Padilla M, et al. Tolerability of integrase inhibitors in a real-life setting. J Antimicrob Chemother. 2017;72(6):1752–1759. doi:10.1093/jac/dkx05328333231
   PubMed Web of Science ®Google Scholar
• Bourgi K, Jenkins C, Rebeiro PF, et al. Greater weight gain among treatment-naive persons starting integrase inhibitors. Conference on Retroviruses and Opportunistic Infections; 2019:Abstract 670 Seattle.
   Google Scholar
• Landovitz RJ, Zangeneh SZ, Chau G, et al. Cabotegravir is not associated with weight gain in HIV-negative individuals: HPTN 077. Conference on Retroviruses and Opportunistic Infections; 2019:Abstract 34 Seattle.
   Google Scholar
• Cohen C, Wohl D, Arribas JR, et al. Week 48 results from a randomized clinical trial of rilpivirine/emtricitabine/tenofovir disoproxil fumarate vs. efavirenz/emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV-1-infected adults. AIDS. 2014;28(7):989–997. doi:10.1097/QAD.000000000000016924508782
   PubMed Web of Science ®Google Scholar
• Llibre JM, Hung -C-C, Brinson C, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018;391(10123):839–849. doi:10.1016/S0140-6736(17)33095-729310899
   PubMed Web of Science ®Google Scholar
• European AIDS Treatment Network Infectious Disease Foundation. WISARD: Switch study mutation rilpivirine dolutegravir. Eu Clinical Trials Register. Available from: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004040-38/ES. Published 2018 Accessed 430, 2019.
   Google Scholar
• Cohen CJ, Molina J-M, Cassetti I, et al. Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials. AIDS. 2013;27(6):939–950. doi:10.1097/QAD.0b013e32835cee6e23211772
   PubMed Web of Science ®Google Scholar
• Yoshinaga T, Seki T, Miki S, et al. Novel secondary mutations C56S and G149A confer resistance to HIV-1 integrase strand transfer inhibitors. Antiviral Res. 2018;152:1–9. doi:10.1016/j.antiviral.2018.01.01329410019
   PubMed Web of Science ®Google Scholar
• Smith SJ, Zhao XZ, Burke TR, Hughes SH. Efficacies of Cabotegravir and Bictegravir against drug-resistant HIV-1 integrase mutants. Retrovirology. 2018;15(1):37. doi:10.1186/s12977-018-0420-729769116
   PubMed Web of Science ®Google Scholar
• Oliveira M, Ibanescu RI, Anstett K, et al. Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Retrovirology. 2018;15(1):1–14. doi:10.1186/s12977-017-0384-z29304821
   PubMed Web of Science ®Google Scholar
• Letendre S, Mills A, Hagins D, et al. Distribution in Cerebrospinal Fluid (CSF) of Cabotegravir (CAB) and Rilpivirine (RPV) after intramuscular administration of long-acting (LA) injectable suspensions in HIV-1-infected patients In: HIV Glasgow. Glasgow; 2018:Abstract 0346 Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1002/jia2.25187
   Google Scholar
• Baril J-G, Angel JB, Gill MJ, et al. Dual therapy treatment strategies for the management of patients infected with HIV: a systematic review of current evidence in ARV-naive or ARV-experienced, virologically suppressed patients. PLoS One. 2016;11(2):e0148231. doi:10.1371/journal.pone.014823126849060
   PubMed Web of Science ®Google Scholar
• Margolis AM, Heverling H, Pham PA, Stolbach A. A review of the toxicity of HIV medications. J Med Toxicol. 2014;10(1):26–39. doi:10.1007/s13181-013-0325-823963694
   PubMedGoogle Scholar
• Orkin C, Llibre J, Gallien S, Antinori A, Behrens G, Carr A. Nucleoside reverse transcriptase inhibitor-reducing strategies in HIV treatment: assessing the evidence. HIV Med. 2018;19(1):18–32. doi:10.1111/hiv.1253428737291
   PubMed Web of Science ®Google Scholar
• Shaik JSB, Ford SL, Lou Y, et al. A phase 1 study to evaluate the pharmacokinetics and safety of cabotegravir in patients with hepatic impairment and healthy matched controls. Clin Pharmacol Drug Dev. Epub Feb 2019.
   Web of Science ®Google Scholar
• Bowers GD, Culp A, Reese MJ, et al. Disposition and metabolism of cabotegravir: a comparison of biotransformation and excretion between different species and routes of administration in humans. Xenobiotica. 2016;46(2):147–162. doi:10.3109/00498254.2015.106037226134155
   PubMed Web of Science ®Google Scholar
• Parasrampuria R, Ford SL, Lou Y, et al. A Phase I study to evaluate the pharmacokinetics and safety of cabotegravir in adults with severe renal impairment and healthy matched control participants. Clin Pharmacol Drug Dev. Epub Feb 2019.
   Web of Science ®Google Scholar
• Lou Y, Buchanan AM, Chen S, et al. Effect of cabotegravir on cardiac repolarization in healthy subjects. Clin Pharmacol Drug Dev. 2016;5(6):509–516. doi:10.1002/cpdd.27227162089
   PubMed Web of Science ®Google Scholar
• Reese MJ, Bowers GD, Humphreys JE, et al. Drug interaction profile of the HIV integrase inhibitor cabotegravir: assessment from in vitro studies and a clinical investigation with midazolam. Xenobiotica. 2016;46(5):445–456. doi:10.3109/00498254.2015.108199326340566
   PubMed Web of Science ®Google Scholar
• Taskar KS, Patel A, Cozens SJ, et al. Prediction of renal OAT1 and OAT3 inhibition by cabotegravir using pbpk modelling. Conference on Retroviruses and Opportunistic Infections; 2019:Abstract 470 Seattle.
   Google Scholar
• Ford SL, Sutton K, Lou Y, et al. Effect of rifampin on the single-dose pharmacokinetics of oral cabotegravir in healthy subjects. Antimicrob Agents Chemother. 2017;61:10. doi:10.1128/AAC.00487-17
   Web of Science ®Google Scholar
• Rajoli RKR, Curley P, Chiong J, et al. Predicting drug–drug interactions between rifampicin and long-acting cabotegravir and rilpivirine using physiologically based pharmacokinetic modeling. J Infect Dis. 2019;219(11):1735–1742. doi:10.1093/infdis/jiy72630566691
   PubMed Web of Science ®Google Scholar
• Trezza C, Ford SL, Gould E, et al. Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol-containing oral contraceptive in healthy adult women. Br J Clin Pharmacol. 2017;83(7):1499–1505. doi:10.1111/bcp.1323628087972
   PubMed Web of Science ®Google Scholar
• Blair C, Li S, Chau G, et al. Hormonal contraceptives do not alter cabotegravir PK in HIV-uninfected women HPTN 077. Conference on Retroviruses and Opportunistic Infections; 2019:Abstract 473 Seattle.
   Google Scholar
• van der Galiën R, Ter Heine R, Greupink R, et al. Pharmacokinetics of HIV-integrase inhibitors during pregnancy: mechanisms, clinical implications and knowledge gaps. Clin Pharmacokinet. 2019;58(3):309–323. doi:10.1007/s40262-018-0684-z29915921
   PubMed Web of Science ®Google Scholar
• Watts DH, Stek A, Best BM, et al. Raltegravir pharmacokinetics during pregnancy. JAIDS J Acquir Immune Defic Syndr. 2014;67(4):375–381. doi:10.1097/QAI.000000000000031825162818
   PubMed Web of Science ®Google Scholar
• Gilleece Y, Tariq S, Bamford A, et al. BHIVA Guidelines on the Management of HIV in Pregnancy and Postpartum. Hertfordshire, United Kingdom: BHIVA Accessed https://www.bhiva.org/pregnancy-guidelines.
   Google Scholar
• Office of AIDS Research Advisory Council. Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States. Maryland, USA: AIDSinfo; 2019 Available from: https://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed April 30, 2019.
   Google Scholar
• Mirochnick M, Shapiro DE, Morrison L, et al. Randomized trial of raltegravir-art vs efavirenz-art when initiated during pregnancy. Conference on Retroviruses and Opportunistic Infections; 2019:Abstract 39 Seattle.
   Google Scholar
• Kintu K, Malaba T, Nakibuka J, et al. rct of dolutegravir vs efavirenz-based therapy initiated in late pregnancy: dolphin-2. Conference on Retroviruses and Opportunistic Infections; 2019 Seattle.
   Google Scholar
• Rajoli RKR, Back DJ, Rannard S, et al. In silico dose prediction for long-acting rilpivirine and cabotegravir administration to children and adolescents. Clin Pharmacokinet. 2018;57(2):255–266. doi:10.1007/s40262-017-0557-x28540638
   PubMed Web of Science ®Google Scholar
• National Institute of Allergy and Infectious Diseases. More Options for Children and Adolescents (MOCHA): oral and long-acting injectable cabotegravir and rilpivirine in HIV-Infected Children and Adolescents (MOCHA). Available from: https://clinicaltrials.gov/ct2/show/NCT03497676?term=MOCHA+HIV&rank=1. Accessed May 2, 2019.
   Google Scholar
• Sherr L, Lampe F, Norwood S, et al. Adherence to antiretroviral treatment in patients with HIV in the UK: a study of complexity. AIDS Care. 2008;20(4):442–448. doi:10.1080/0954012070186703218449821
   PubMed Web of Science ®Google Scholar
• Heestermans T, Browne JL, Aitken SC, Vervoort SC, Klipstein-Grobusch K. Determinants of adherence to antiretroviral therapy among HIV-positive adults in sub-Saharan Africa: a systematic review. BMJ Glob Heal. 2016;1(4):e000125. doi:10.1136/bmjgh-2016-000125
   PubMed Web of Science ®Google Scholar
• Costa JDM, Torres TS, Coelho LE, Luz PM. Adherence to antiretroviral therapy for HIV/AIDS in Latin America and the Caribbean: systematic review and meta-analysis. J Int AIDS Soc. 2018;21(1):e25066. doi:10.1002/jia2.25066
   Web of Science ®Google Scholar
• Langebeek N, Gisolf EH, Reiss P, et al. Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis. BMC Med. 2014;12:142. doi:10.1186/s12916-014-0141-225145556
   PubMed Web of Science ®Google Scholar
• Jackson A, Mcgowan I. Long-acting rilpivirine for HIV prevention. Curr Opin HIV AIDS. 2015;10(4):253–257. doi:10.1097/COH.000000000000016026049950
   PubMed Web of Science ®Google Scholar
• ViiV Healthcare. Efficacy, safety and tolerability study of long-acting cabotegravir plus long-acting rilpivirine (CAB LA + RPV LA) in human-immunodeficiency virus-1 (HIV-1) infected adults. Available from: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03299049?term=Efficacy%2C+Safety+and+Tolerability+Study+of+Long-acting+Cabotegravir+Plus+Long-acting+Rilpivirine+%28CAB+LA+%2B+RPV+LA%29+in+Human-immunodeficiency+Virus-1+%28HIV-1%29+Infected+Adults&rank=1. Published 2018 Accessed 430, 2019.
   Google Scholar
• National Institute of Allergy and Infectious Diseases. The latitude Study: long-acting therapy to improve treatment success in daily life. ClinicalTrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT03635788?term=NCT03635788&rank=1. Published 2019 Accessed 430, 2019.
   Google Scholar