Pettoello-Mantovani M, Kollmann T R, Katopodis N F, Raker C, Kim A, Yurasov S, Wiltshire H, Goldstein H
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Infect Dis. 1998 Feb;177(2):337-46. doi: 10.1086/514214.
Modified, human immunodeficiency virus (HIV)-inoculated thy/liv-SCID-hu mice were used to evaluate the in vivo efficacy of antiretroviral drugs. Ritonavir treatment alone initially suppressed plasma viremia, but the viremia recurred with the appearance of ritonavir-resistant HIV isolates. Multidrug therapy suppressed plasma HIV RNA to undetectable levels; however, plasma viremia returned after therapy was stopped, showing that the therapy did not completely suppress HIV infection in the thymic implant. When thy/liv-SCID-hu mice were treated with a combination of zidovudine, lamivudine, and ritonavir immediately after inoculation with HIV, cocultures of the thymic implants remained negative for HIV even 1 month after therapy was discontinued, suggesting that acute treatment can prevent the establishment of HIV infection. Thus, these modified thy/liv-SCID-hu mice should prove to be a useful system for evaluating the effectiveness of different antiretroviral therapies on acute and chronic HIV infection.
使用经修饰的接种了人类免疫缺陷病毒(HIV)的thy/liv-SCID-hu小鼠来评估抗逆转录病毒药物的体内疗效。单独使用利托那韦治疗最初可抑制血浆病毒血症,但随着利托那韦耐药HIV毒株的出现,病毒血症复发。联合药物治疗可将血浆HIV RNA抑制到检测不到的水平;然而,治疗停止后血浆病毒血症又复发,表明该治疗并未完全抑制胸腺植入物中的HIV感染。当thy/liv-SCID-hu小鼠在接种HIV后立即用齐多夫定、拉米夫定和利托那韦联合治疗时,即使在治疗停止1个月后,胸腺植入物的共培养物对HIV仍呈阴性,这表明急性治疗可预防HIV感染的建立。因此,这些经修饰的thy/liv-SCID-hu小鼠应被证明是评估不同抗逆转录病毒疗法对急性和慢性HIV感染有效性的有用系统。