Vadlapudi Aswani D, Vadlapatla Ramya K, Mitra Ashim K
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108-2718, USA.
Recent Pat Antiinfect Drug Discov. 2012 Apr;7(1):8-18. doi: 10.2174/157489112799829765.
Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic complication and a serious cause of vision loss in immunocompromised patients. Even though, a rise in human immunodeficiency virus (HIV) infected individuals seems to be a major factor responsible for the prevalence of CMV retinitis, the introduction of highly active antiretroviral therapy (HAART) significantly reduced the incidence and severity of CMV retinitis. Thorough evaluation of the patient's immune status and an exact classification of the retinal lesions may provide better understanding of the disease etiology, which would be necessary for optimizing the treatment conditions. Current drugs such as ganciclovir, valganciclovir, cidofovir and foscarnet have been highly active against CMV, but prolonged therapy with these approved drugs is associated with dose-limiting toxicities thus limiting their utility. Moreover development of drug-resistant mutants has been observed particularly in patients with acquired immunodeficiency syndrome (AIDS). Continuous efforts by researchers in the industry and academia have led to the development of newer candidates with enhanced antiviral efficacy and apparently minimal side effects. These novel compounds can suppress viral replication and prevent reactivation in the target population. Though some of the novel therapeutics possess potent viral inhibitory activity, these compounds are still in stages of clinical development and yet to be approved. This review provides an overview of disease etiology, existing anti-CMV drugs, advances in emerging therapeutics in clinical development and related recent patents for the treatment of CMV retinitis.
巨细胞病毒(CMV)视网膜炎是免疫功能低下患者中最常见的眼部机会性并发症,也是导致视力丧失的严重原因。尽管人类免疫缺陷病毒(HIV)感染个体数量的增加似乎是CMV视网膜炎患病率上升的主要因素,但高效抗逆转录病毒疗法(HAART)的引入显著降低了CMV视网膜炎的发病率和严重程度。对患者免疫状态进行全面评估以及对视网膜病变进行准确分类,可能有助于更好地理解疾病病因,这对于优化治疗条件至关重要。目前的药物如更昔洛韦、缬更昔洛韦、西多福韦和膦甲酸钠对CMV具有高度活性,但长期使用这些获批药物会出现剂量限制性毒性,从而限制了它们的效用。此外,特别是在获得性免疫缺陷综合征(AIDS)患者中观察到了耐药突变体的产生。业内和学术界研究人员的持续努力促成了具有更高抗病毒疗效且副作用明显最小的新型候选药物的开发。这些新型化合物可以抑制病毒复制并防止目标人群中的病毒重新激活。尽管一些新型疗法具有强大的病毒抑制活性,但这些化合物仍处于临床开发阶段,尚未获批。本综述概述了CMV视网膜炎的疾病病因、现有的抗CMV药物、临床开发中新兴疗法的进展以及相关的近期治疗专利。