Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials
Objectives: To investigate the safety and pharmacokinetic profiles of long-acting injectable pre-exposure prophylaxis (LAI PrEP), notably cabotegravir (CAB-LA) and rilpivirine (RPV-LA), for the prevention of human immunodeficiency virus-1 (HIV-1) infection.Methods: Eligible randomized trials of LAI...
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| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.664875/full |
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| author | Gilbert Lazarus Vincent Kharisma Wangsaputra Christianto Melva Louisa Vivian Soetikno Raph L. Hamers Raph L. Hamers Raph L. Hamers |
| author_facet | Gilbert Lazarus Vincent Kharisma Wangsaputra Christianto Melva Louisa Vivian Soetikno Raph L. Hamers Raph L. Hamers Raph L. Hamers |
| author_sort | Gilbert Lazarus |
| collection | DOAJ |
| description | Objectives: To investigate the safety and pharmacokinetic profiles of long-acting injectable pre-exposure prophylaxis (LAI PrEP), notably cabotegravir (CAB-LA) and rilpivirine (RPV-LA), for the prevention of human immunodeficiency virus-1 (HIV-1) infection.Methods: Eligible randomized trials of LAI PrEP in HIV-uninfected and/or healthy patients were included and assessed with the Revised Cochrane risk-of-bias tool for randomized trials. Where feasible, a meta-analysis was performed for safety outcomes by using a random-effects model with risk ratios and their 95% confidence intervals as the common effect measure. The protocol was registered with PROSPERO CRD42020154772.Results: Eight studies cumulating a total of 666 participants were included in this systematic review, including five (362 intervention-arm volunteers) and four trials (194 intervention-arm volunteers) that investigated CAB-LA and RPV-LA, respectively. We found that both CAB-LA and RPV-LA were generally well-tolerated as their safety profiles were similar to placebo in terms of any adverse event (AE), serious AE, and AE-related withdrawals. Furthermore, pharmacokinetic analyses revealed favorable prospects in viral inhibitory activity of CAB-LA and RPV-LA. Intramuscular (IM) injection of CAB-LA 600 mg Q8W was superior to CAB-LA 800 mg Q12W in male participants, while the same was true for RPV-LA 1200 mg IM Q8W over other dosing regimens. Although these results are promising, further research is required to confirm the findings on RPV-LA as current evidence is limited.Conclusion: CAB-LA and RPV-LA have promising safety and pharmacokinetic profiles. The preventive efficacy of these agents is being evaluated in Phase 3 trials. |
| first_indexed | 2024-12-19T05:51:58Z |
| format | Article |
| id | doaj.art-f3505cd3d53348668c02e084644a2827 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T05:51:58Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f3505cd3d53348668c02e084644a28272022-12-21T20:33:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-07-011210.3389/fphar.2021.664875664875Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized TrialsGilbert Lazarus0Vincent Kharisma Wangsaputra1 Christianto2Melva Louisa3Vivian Soetikno4Raph L. Hamers5Raph L. Hamers6Raph L. Hamers7Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaFaculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaFaculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaDepartment of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaDepartment of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaFaculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaEijkman-Oxford Clinical Research Unit, Jakarta, IndonesiaCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomObjectives: To investigate the safety and pharmacokinetic profiles of long-acting injectable pre-exposure prophylaxis (LAI PrEP), notably cabotegravir (CAB-LA) and rilpivirine (RPV-LA), for the prevention of human immunodeficiency virus-1 (HIV-1) infection.Methods: Eligible randomized trials of LAI PrEP in HIV-uninfected and/or healthy patients were included and assessed with the Revised Cochrane risk-of-bias tool for randomized trials. Where feasible, a meta-analysis was performed for safety outcomes by using a random-effects model with risk ratios and their 95% confidence intervals as the common effect measure. The protocol was registered with PROSPERO CRD42020154772.Results: Eight studies cumulating a total of 666 participants were included in this systematic review, including five (362 intervention-arm volunteers) and four trials (194 intervention-arm volunteers) that investigated CAB-LA and RPV-LA, respectively. We found that both CAB-LA and RPV-LA were generally well-tolerated as their safety profiles were similar to placebo in terms of any adverse event (AE), serious AE, and AE-related withdrawals. Furthermore, pharmacokinetic analyses revealed favorable prospects in viral inhibitory activity of CAB-LA and RPV-LA. Intramuscular (IM) injection of CAB-LA 600 mg Q8W was superior to CAB-LA 800 mg Q12W in male participants, while the same was true for RPV-LA 1200 mg IM Q8W over other dosing regimens. Although these results are promising, further research is required to confirm the findings on RPV-LA as current evidence is limited.Conclusion: CAB-LA and RPV-LA have promising safety and pharmacokinetic profiles. The preventive efficacy of these agents is being evaluated in Phase 3 trials.https://www.frontiersin.org/articles/10.3389/fphar.2021.664875/fullcabotegravirlong acting injectable (LAI)HIV-human immunodeficiency viruspre-exposure (PrEP) prophylaxisrilpivirine |
| spellingShingle | Gilbert Lazarus Vincent Kharisma Wangsaputra Christianto Melva Louisa Vivian Soetikno Raph L. Hamers Raph L. Hamers Raph L. Hamers Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials Frontiers in Pharmacology cabotegravir long acting injectable (LAI) HIV-human immunodeficiency virus pre-exposure (PrEP) prophylaxis rilpivirine |
| title | Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials |
| title_full | Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials |
| title_fullStr | Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials |
| title_full_unstemmed | Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials |
| title_short | Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials |
| title_sort | safety and pharmacokinetic profiles of long acting injectable antiretroviral drugs for hiv 1 pre exposure prophylaxis a systematic review and meta analysis of randomized trials |
| topic | cabotegravir long acting injectable (LAI) HIV-human immunodeficiency virus pre-exposure (PrEP) prophylaxis rilpivirine |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.664875/full |
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