Mbhele Nokuzola, Chimukangara Benjamin, Gordon Michelle
KwaZulu-Natal Research, Innovation and Sequencing Platform (KRISP), College of Health Sciences, University of KwaZulu-Natal, Doris Duke Medical Research Institute, Durban, South Africa.
KwaZulu-Natal Research, Innovation and Sequencing Platform (KRISP), College of Health Sciences, University of KwaZulu-Natal, Doris Duke Medical Research Institute, Durban, South Africa; Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa; Department of Virology, National Health Laboratory Service, University of KwaZulu-Natal, Durban, South Africa.
Int J Antimicrob Agents. 2021 May;57(5):106343. doi: 10.1016/j.ijantimicag.2021.106343. Epub 2021 Apr 11.
Antiretroviral therapy has been imperative in controlling the human immunodeficiency virus (HIV) epidemic. Most low- and middle-income countries have used nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors extensively in the treatment of HIV. However, integrase strand transfer inhibitors (INSTIs) are becoming more common. Since their identification as a promising therapeutic drug, significant progress has been made that has led to the approval of five INSTIs by the US Food and Drug Administration (FDA), i.e. dolutegravir (DTG), raltegravir (RAL), elvitegravir (EVG), bictegravir (BIC) and cabotegravir (CAB). INSTIs have been shown to effectively halt HIV-1 replication and are commended for having a higher genetic barrier to resistance compared with NRTIs and NNRTIs. More interestingly, DTG has shown a higher genetic barrier to resistance compared with RAL and EVG, and CAB is being used as the first long-acting agent in HIV-1 treatment. Considering the increasing interest in INSTIs for HIV-1 treatment, we focus our review on the retroviral integrase, development of INSTIs and their mode of action. We also discuss each of the INSTI drugs, including potential drug resistance and known side effects.
抗逆转录病毒疗法对于控制人类免疫缺陷病毒（HIV）流行至关重要。大多数低收入和中等收入国家在治疗HIV时广泛使用了核苷类逆转录酶抑制剂（NRTIs）、非核苷类逆转录酶抑制剂（NNRTIs）和蛋白酶抑制剂。然而，整合酶链转移抑制剂（INSTIs）正变得越来越普遍。自从它们被认定为一种有前景的治疗药物以来，已经取得了重大进展，导致美国食品药品监督管理局（FDA）批准了五种INSTIs，即多替拉韦（DTG）、拉替拉韦（RAL）、埃替拉韦（EVG）、比克替拉韦（BIC）和卡博特韦（CAB）。INSTIs已被证明能有效阻止HIV-1复制，并且因其与NRTIs和NNRTIs相比具有更高的耐药基因屏障而受到称赞。更有趣的是，与RAL和EVG相比，DTG显示出更高的耐药基因屏障，并且CAB正被用作HIV-1治疗中的首个长效药物。鉴于对INSTIs用于HIV-1治疗的兴趣日益增加，我们将综述重点放在逆转录病毒整合酶、INSTIs的开发及其作用方式上。我们还将讨论每种INSTI药物，包括潜在的耐药性和已知的副作用。
