Floridia M, Tomino C, Bucciardini R, Ricciardulli D, Fragola V, Pirillo M F, Amici R, Giannini G, Galluzzo C M, Andreotti M, Seeber A C, Ammassari A, Cingolani A, Lazzarin A, Scalise G, Cargnel A, Suter F, Milazzo F, Pastore G, Moroni M, Ciammarughi R, Pini R, Carosi G, D'Amato C, Contu L, Concia E, Bonazzi L, Aiuti F, Vigevani G, Vella S
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
AIDS Res Hum Retroviruses. 2000 Nov 20;16(17):1809-20. doi: 10.1089/08892220050195775.
ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).
ISS - IP1是一项多中心、随机、为期48周的开放试验，旨在比较对既往有核苷类药物治疗经历且CD4 + 细胞计数低于50/mm³ 的患者使用利托那韦或茚地那韦的情况。允许同时使用核苷类似物进行抗逆转录病毒治疗。主要疗效指标为生存率以及出现新的艾滋病定义事件或死亡的时间，采用意向性分析方法在整个观察期内进行分析。主要毒性指标为治疗中断时间和至少3级/严重不良事件，采用治疗中分析方法进行分析。疗效评估还包括CD4 + 细胞和RNA反应。该试验在5个月内招募了1251名患者。基线时，两组的平均CD4 + 细胞计数约为20个细胞/mm³，平均HIV RNA拷贝数为4.9 log10/ml。总体而言，利托那韦组有402名患者、茚地那韦组有250名患者永久停止了分配的治疗（相对风险，1.96；95%可信区间，1.68 - 2.30；p = 0.0001），这种差异大部分归因于利托那韦组因不良事件导致的停药人数较多。在平均随访307天（利托那韦组304天，茚地那韦组309天）后，观察到有124例死亡（利托那韦组61例，茚地那韦组63例；相对风险，0.96；95%可信区间，0.67 - 1.36；p = 0.80）以及330例新的艾滋病定义事件（利托那韦组170例，茚地那韦组160例；相对风险，1.05；95%可信区间，0.85 - 1.31；p = 0.60）。仍在接受治疗的患者中，两组的CD4 + 细胞计数均有所增加，到第24周时增加了约100个细胞，到第48周时增加了150个细胞。两组患者的体重也随时间增加。RNA反应分析显示两个治疗组均下降了1.5 log10或更多。总体而言，利托那韦组有400名患者、茚地那韦组有338名患者在随访期间出现了至少1次3级/严重新不良事件（相对风险，1.48；95%可信区间，1.28 - 1.72；p = 0.0001）。继续接受治疗的两组患者在第24周和第48周时均观察到了良好的CD4 + 细胞和RNA反应。茚地那韦在维持RNA、CD4 + 细胞和体重反应方面显示出稍好的效果。在临床结局（生存率和艾滋病定义事件）方面，利托那韦和茚地那韦的结果相当。
