Calcagno Andrea, Montrucchio Chiara, Capetti Amedeo, Guaraldi G, Cenderello G, Calza Leonardo, Lanzafame M, Marinaro Letizia, Tettoni M C, Trentini Laura, D'Avolio Aantonio, Di Perri Giovanni, Bonora Stefano
Clinica Univesitaria di Malattie Infettive, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy.
Curr HIV Res. 2016;14(1):54-60. doi: 10.2174/1570162x13666150929112135.
Tolerability, long-term toxicities and selection of resistant variants limit the use and efficacy of antiretroviral drugs in HIV-positive patients. Novel combinations are needed for mantaining long-term control of HIV replication; nevertheless scarse data are available on protease inhibitor-free dual antiretroviral therapies.
A multi-centric retrospective study was conducted including HIV-1-positive patients on raltegravir/nevirapine dual regimens. Plasma concentrations were measured as therapeutic drug monitoring while a subset of patients underwent intensive 12-hour pharmacokinetic evaluation.
A total of 77 patients switching from successful regimens (76.6% male, median age 52 years) was included; 10 patients on raltegravir plus nevirapine once-daily while 67 subjects on twice-daily schedule. After a median follow-up of 32 months 69 patients (89.6%) were still successfully on treatment. Three patients discontinued for side effects (skin rash or hepatoxicity). Virological failure was observed in five patients (6.5%, 3 on once-daily schedule): in 4 patients (80%) resistance-associated mutations were observed (4 reverse transcriptase, 2 integrase). Triglycerides decreased in patients switching with lipid abnormalities (n=52) and estimated creatinine clearance increased in those with less than 60 ml/min (n=13). Median trough raltegravir and nevirapine concentrations were 83 ng/ml (32-227) and 5460 ng/ml (4037-7221); intensive 12-hours pharmacokinetic parameters (n=7) were similar to published data.
Dual therapy with raltegravir/nevirapine in selected patients was highly effective over a 32-month follow up: virological failure was infrequent (6.5%), most common with once-daily schedule (60%) and often associated with the selection of resistance-associated mutations (80%). Twice-daily raltegravir plus nevirapine deserves further clinical evaluation as an NRTI- and PI-sparing strategy in selected patients.
耐受性、长期毒性以及耐药变异体的选择限制了抗逆转录病毒药物在HIV阳性患者中的使用和疗效。需要新型联合用药方案来维持对HIV复制的长期控制；然而，关于不含蛋白酶抑制剂的双药抗逆转录病毒疗法的数据却很少。
开展了一项多中心回顾性研究，纳入接受拉替拉韦/奈韦拉平双药方案治疗的HIV-1阳性患者。通过治疗药物监测测定血浆浓度，同时对一部分患者进行了为期12小时的强化药代动力学评估。
共纳入77例从成功方案转换治疗的患者（76.6%为男性，中位年龄52岁）；10例患者接受拉替拉韦加奈韦拉平每日一次治疗，67例患者接受每日两次治疗。中位随访32个月后，69例患者（89.6%）仍成功接受治疗。3例患者因副作用（皮疹或肝毒性）停药。5例患者（6.5%）出现病毒学失败（每日一次治疗方案中有3例）：4例患者（80%）观察到与耐药相关的突变（4例逆转录酶突变，2例整合酶突变）。脂质异常患者转换治疗后甘油三酯水平降低（n = 52），肌酐清除率估计值低于60 ml/min的患者肌酐清除率升高（n = 13）。拉替拉韦和奈韦拉平的中位谷浓度分别为83 ng/ml（32 - 227）和5460 ng/ml（4037 - 7221）；强化12小时药代动力学参数（n = 7）与已发表数据相似。
在选定患者中，拉替拉韦/奈韦拉平双药疗法在32个月的随访中疗效显著：病毒学失败发生率低（6.5%），最常见于每日一次治疗方案（60%），且常与耐药相关突变的选择有关（80%）。每日两次的拉替拉韦加奈韦拉平作为一种在选定患者中节省核苷类逆转录酶抑制剂和蛋白酶抑制剂的策略，值得进一步临床评估。
