Romanelli Frank, Smith Kelly M, Hoven Ardis Dee
University of Kentucky College of Pharmacy, 800 Rose Street, Lexington, KY 40536, USA.
Curr Pharm Des. 2004;10(21):2643-8. doi: 10.2174/1381612043383791.
Recent advances in the development of antiretrovirals have significantly extended life-spans and positively impacted morbidity of HIV-seropositive patients. While effective, antiretrovirals are associated with complex medication regimens, large pill burdens, and significant side effects which may impact quality of life. Researchers continue to examine various chemical entities in their search for agents with anti-HIV activity. Ideal agents would be efficacious, easily dosed and administered, inexpensive, and with few adverse effects. Chloroquine and its analog hydroxychloroquine are two inexpensive agents that are widely used for the treatment of malaria and have been shown to achieve some level of anti-HIV activity. The exact mechanism of chloroquine and hydroxychloroquine's anti-HIV activity has not yet been discerned but may be related to effects on HIV's surface envelope glycoprotein 120. If found efficacious, both drugs would offer significant advantages to current therapy including a unique mechanism of action, lack of cross-resistance with other antiretrovirals, and low cost. Early and limited in vitro and in vivo data have demonstrated modest anti-HIV efficacy as indicated by measures of viral burden. Effects on CD4+ cell counts have not been as pronounced. It is premature to advocate the use of either of these agents in the management of routine HIV disease; however; the drugs should be further studied to determine their benefit in the treatment of patients who have exhausted all standard treatments. Larger, well-controlled trials are needed to discern the potential role of chloroquine and hydroxychloroquine in the management of HIV.
抗逆转录病毒药物研发的最新进展显著延长了HIV血清阳性患者的寿命，并对其发病率产生了积极影响。虽然抗逆转录病毒药物有效，但它们与复杂的用药方案、大量的 pill负担以及可能影响生活质量的显著副作用相关。研究人员继续研究各种化学实体，以寻找具有抗HIV活性的药物。理想的药物应该有效、易于给药、价格低廉且副作用少。氯喹及其类似物羟氯喹是两种价格低廉的药物，广泛用于治疗疟疾，并且已显示出一定程度的抗HIV活性。氯喹和羟氯喹抗HIV活性的确切机制尚未明确，但可能与对HIV表面包膜糖蛋白120的作用有关。如果发现有效，这两种药物将为当前治疗带来显著优势，包括独特的作用机制、与其他抗逆转录病毒药物无交叉耐药性以及成本低。早期有限的体外和体内数据表明，通过病毒载量测量显示出适度的抗HIV疗效。对CD4 +细胞计数的影响并不那么明显。在常规HIV疾病管理中提倡使用这两种药物中的任何一种都为时过早；然而，应该对这些药物进行进一步研究，以确定它们在治疗用尽所有标准治疗的患者中的益处。需要进行更大规模、严格控制的试验，以确定氯喹和羟氯喹在HIV管理中的潜在作用。
