Koup R A, Brewster F, Grob P, Sullivan J L
University of Massachusetts Medical School, Department of Pediatrics, Worcester.
AIDS. 1993 Sep;7(9):1181-4. doi: 10.1097/00002030-199309000-00005.
To determine whether synergistic inhibition of HIV-1 replication would result from the in vitro use of nevirapine in combination with zidovudine, interferon (IFN)-alpha 2C, and CD4 immunoadhesin.
The non-nucleoside reverse transcriptase inhibitor nevirapine (formerly BI-RG-587) was tested in combination with the other antiretrovial agents. Assays were performed on stimulated peripheral blood lymphocytes infected with HIV-1. Virus replication was assessed by the release of viral p24 antigen into culture supernatants. The median-effect principle was used to assess for synergistic interactions of the combined agents.
Zidovudine, IFN-alpha 2C and CD4 immunoadhesin, when used in combination with nevirapine, synergistically inhibited HIV-1 replication in human peripheral blood lymphocytes compared with each agent used alone. Some analyses were also consistent with additive effects, but antagonism was not noted.
These in vitro findings provide a scientific basis for future trials with similar drug combinations.
确定在体外将奈韦拉平与齐多夫定、干扰素(IFN)-α 2C和CD4免疫粘附素联合使用是否会产生对HIV-1复制的协同抑制作用。
对非核苷类逆转录酶抑制剂奈韦拉平(原BI-RG-587)与其他抗逆转录病毒药物的联合使用进行了测试。对感染HIV-1的外周血淋巴细胞进行了检测。通过病毒p24抗原释放到培养上清液中来评估病毒复制。采用中位效应原理评估联合用药的协同相互作用。
与单独使用每种药物相比,齐多夫定、IFN-α 2C和CD4免疫粘附素与奈韦拉平联合使用时,能协同抑制人外周血淋巴细胞中的HIV-1复制。一些分析也与相加作用一致,但未发现拮抗作用。
这些体外研究结果为未来使用类似药物组合进行试验提供了科学依据。