Demeter L M, Meehan P M, Morse G, Gerondelis P, Dexter A, Berrios L, Cox S, Freimuth W, Reichman R C
Infectious Diseases Unit, University of Rochester, New York 14642, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Feb 1;14(2):136-44. doi: 10.1097/00042560-199702010-00006.
Previous studies have shown that the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase mutation Y181C, which confers high-level resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), develops rarely during therapy with NNRTIs plus zidovudine. To determine whether didanosine (ddI) is also effective in preventing the emergence of Y181C, we analyzed delavirdine (DLV) susceptibilties and reverse transcriptase sequences of isolates obtained from patients enrolled in a pharmacokinetic study of DLV and ddI. Nine NNRTI-naive patients were evaluated. Seven received DLV/ddI and two received DLV/ddI/zidovudine. Median durations of prior zidovudine and ddI were 26 and 15 months, respectively. Isolates from eight of nine patients had a mutation(s) associated with nucleoside resistance at entry. After treatment with DLV and ddI alone, isolates from five of seven patients developed Y181C, four in combination with K103N. Thus, in this group of nucleoside-experienced patients, combination therapy with DLV/ddI did not prevent the emergence of Y181C.
先前的研究表明，1型人类免疫缺陷病毒（HIV-1）逆转录酶突变Y181C可赋予对非核苷类逆转录酶抑制剂（NNRTIs）的高水平耐药性，在使用NNRTIs加齐多夫定治疗期间很少出现。为了确定去羟肌苷（ddI）是否也能有效预防Y181C的出现，我们分析了从参与去羟肌苷和ddI药代动力学研究的患者中分离出的病毒株的地拉韦啶（DLV）敏感性和逆转录酶序列。对9名未接受过NNRTIs治疗的患者进行了评估。7名患者接受DLV/ddI治疗，2名患者接受DLV/ddI/齐多夫定治疗。先前齐多夫定和ddI的中位治疗时间分别为26个月和15个月。9名患者中有8名患者的分离株在初治时存在与核苷类耐药相关的突变。在单独使用DLV和ddI治疗后，7名患者中有5名患者的分离株出现了Y181C，其中4名患者同时伴有K103N突变。因此，在这组有核苷类治疗经验的患者中，DLV/ddI联合治疗未能预防Y181C的出现。
