{"title":"用于预防艾滋病的长效注射用卡博替拉韦(Cabotegravir):我们对卡博特拉韦耐药性的风险和后果了解多少?","authors":"Urvi M Parikh, Catherine A Koss, John W Mellors","doi":"10.1007/s11904-022-00616-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Cabotegravir is a potent integrase strand transfer inhibitor (INSTI) recently approved as a long-acting injectable formulation for HIV prevention (CAB-LA). We summarize what is known about cabotegravir pharmacokinetics, activity, and emergence of resistance from in vitro, macaque and clinical studies, and we evaluate the risk of resistance from CAB-LA with on-time injections and after CAB-LA discontinuation.</p><p><strong>Recent findings: </strong>The accumulation of multiple INSTI mutations is required for high-level cabotegravir resistance, and the same mutation combinations may cause cross-resistance to dolutegravir, which is widely used for first-line antiretroviral therapy in low- and middle-income countries. Though CAB-LA was highly effective in preventing HIV, breakthrough infections did occur in trials of CAB-LA despite on-time injections, resulting in selection of single and combinations of INSTI resistance mutations. As CAB-LA is scaled-up, prompt HIV diagnosis to prevent resistance, and resistance monitoring could help preserve the effectiveness of INSTIs for both HIV treatment and prevention.</p>","PeriodicalId":10930,"journal":{"name":"Current HIV/AIDS Reports","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508028/pdf/","citationCount":"0","resultStr":"{\"title\":\"Long-Acting Injectable Cabotegravir for HIV Prevention: What Do We Know and Need to Know about the Risks and Consequences of Cabotegravir Resistance?\",\"authors\":\"Urvi M Parikh, Catherine A Koss, John W Mellors\",\"doi\":\"10.1007/s11904-022-00616-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose of review: </strong>Cabotegravir is a potent integrase strand transfer inhibitor (INSTI) recently approved as a long-acting injectable formulation for HIV prevention (CAB-LA). We summarize what is known about cabotegravir pharmacokinetics, activity, and emergence of resistance from in vitro, macaque and clinical studies, and we evaluate the risk of resistance from CAB-LA with on-time injections and after CAB-LA discontinuation.</p><p><strong>Recent findings: </strong>The accumulation of multiple INSTI mutations is required for high-level cabotegravir resistance, and the same mutation combinations may cause cross-resistance to dolutegravir, which is widely used for first-line antiretroviral therapy in low- and middle-income countries. Though CAB-LA was highly effective in preventing HIV, breakthrough infections did occur in trials of CAB-LA despite on-time injections, resulting in selection of single and combinations of INSTI resistance mutations. As CAB-LA is scaled-up, prompt HIV diagnosis to prevent resistance, and resistance monitoring could help preserve the effectiveness of INSTIs for both HIV treatment and prevention.</p>\",\"PeriodicalId\":10930,\"journal\":{\"name\":\"Current HIV/AIDS Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2022-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508028/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current HIV/AIDS Reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11904-022-00616-y\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/9/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current HIV/AIDS Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11904-022-00616-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/9/16 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
摘要
综述目的:卡博特拉韦是一种强效整合酶链转移抑制剂(INSTI),最近被批准为预防艾滋病的长效注射制剂(CAB-LA)。我们总结了体外、猕猴和临床研究中有关卡博特拉韦药代动力学、活性和耐药性产生的已知信息,并评估了按时注射 CAB-LA 和停用 CAB-LA 后产生耐药性的风险:在中低收入国家,多鲁曲韦被广泛用于一线抗逆转录病毒治疗。尽管 CAB-LA 在预防 HIV 方面非常有效,但在 CAB-LA 的试验中,尽管按时注射,仍发生了突破性感染,导致 INSTI 单个或组合耐药突变的选择。随着 CAB-LA 的推广,及时进行 HIV 诊断以防止耐药性的产生以及耐药性监测有助于保持 INSTIs 在 HIV 治疗和预防方面的有效性。
Long-Acting Injectable Cabotegravir for HIV Prevention: What Do We Know and Need to Know about the Risks and Consequences of Cabotegravir Resistance?
Purpose of review: Cabotegravir is a potent integrase strand transfer inhibitor (INSTI) recently approved as a long-acting injectable formulation for HIV prevention (CAB-LA). We summarize what is known about cabotegravir pharmacokinetics, activity, and emergence of resistance from in vitro, macaque and clinical studies, and we evaluate the risk of resistance from CAB-LA with on-time injections and after CAB-LA discontinuation.
Recent findings: The accumulation of multiple INSTI mutations is required for high-level cabotegravir resistance, and the same mutation combinations may cause cross-resistance to dolutegravir, which is widely used for first-line antiretroviral therapy in low- and middle-income countries. Though CAB-LA was highly effective in preventing HIV, breakthrough infections did occur in trials of CAB-LA despite on-time injections, resulting in selection of single and combinations of INSTI resistance mutations. As CAB-LA is scaled-up, prompt HIV diagnosis to prevent resistance, and resistance monitoring could help preserve the effectiveness of INSTIs for both HIV treatment and prevention.
期刊介绍:
This journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of HIV/AIDS.
We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as antiretroviral therapies, behavioral aspects of management, and metabolic complications and comorbidity. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.