IV OR SQRHIL2 IN HIV INFECTED SUBJECTS ON HAART

这项研究的基本假设是，与单独使用高效抗逆转录病毒疗法相比，采用高效抗逆转录病毒疗法的不同间歇给药途径(静脉注射和皮下给药)在受试者一年后CD4计数比随机前基线增加50%的比例和CD4计数的变化率方面存在差异。这项研究还将测试这些方案的安全性、耐受性和对生活质量的影响是否存在差异，以及与单独使用HAART相比，HAART在免疫细胞表型和功能、HIV病毒载量和抗病毒耐药性发展速度方面是否有可测量的变化。方法：这是一项随机研究，目的是确定持续静脉注射高剂量间歇注射重组人白介素2与皮下注射联合高效抗逆转录病毒治疗与单独应用高效抗逆转录病毒治疗对HIV患者的CD4反应的影响。受试者必须对蛋白水解酶抑制剂进行幼稚治疗。所有受试者都将接受吲地那韦和两种核苷类似物的治疗；其中一种对受试者来说是新的(HAART)。受试者将接受12周的HAART。在第10周，将由CHIRON完成BDNA的HIV RNA(实时)检测。携带&lt；5000拷贝/毫升的受试者将继续研究。携带&gt；5000拷贝/毫升的受试者将不需要进一步的随访，应该停止研究。然后，将HIV RNA拷贝数为5000拷贝/毫升的受试者随机分为两组，一组继续HAART，或联合HAART，每8周持续输注900万单位(CIV)，持续5天，共72周，或9个周期；或皮下注射rhIL-2 750万单位，每天两次，每8周5天，共72周，或9个周期。接受CIV治疗的受试者，如果在3个周期或6个周期后，CD4细胞数均较随机前基准值增加25%且至少增加100cell/mm3，则在剩下的疗程中，每天两次皮下注射重组人IL-2，每8周皮下注射5天。结果和未来计划：研究仍在进行中，治疗组仍处于盲目状态，因此研究结论和意义尚不能讨论。这项研究正在继续招募患者，并将继续这样做，直到达到国家招募目标。意义：对于许多HIV感染者来说，改善免疫功能仍然是一个虚幻的目标。这项研究将有助于为艾滋病毒感染患者开发免疫恢复性疗法。

The primary hypothesis of this study is that there will be a difference between different routes of intermittently administered rhIL-2 (IV vs subcutaneous admininistration) with a highly active antiretroviral regimen compared to highly active antiretroviral therapy alone with respect to the proportion of subjects achieving 50% increase in CD4 counts above pre-randomization baseline values after one year of rhIL-2 and the rate of change in CD4 counts. The study will also test whether there is a difference between the safety, tolerance, and effect on quality of life of these regimensand whether there are measureable changes in immune cell phenotypes and function and on HIV viral load and rate of antiviral drug resistance development when HAART is used in the setting of rhIL-2 compared to HAART alone. Methods: This is a randomized study to ascertain the effect on CD4 response of high dose, intermittently administered rhIL-2 administered by continuous intravenous infusion versus subcutaneous injections in conjunction with highly active antiretroviral therapy versus highly active antiretroviral therapy alone in patients with HIV and CD4 counts of 50- 300 cells/mm3. Subjects must be protease inhibitor therapy naive. All subjects will receive treatment with indinavir and 2 nucleoside analogues; one of which is new to the subject (HAART). Subjects will receive 12 weeks of HAART. At week 10 an HIV RNA by bDNA (real time) will be done by Chiron. Subjects with < 5,000 copies/ml will be continued on study. Subjects with > 5,000 copies/ml will require no further follow-up and should be taken off study. Subjects who have <5,000 copies/ml of HIV RNA will then be randomized to continue HAART alone or HAART with rhIL-2 at either 9 million units by continuous infusion (CIV) for 5 days every 8 weeks for 72 weeks, or 9 cycles, or rhIL-2 at 7.5 million units by subcutaneous injection twice a day for 5 days every 8 weeks for 72 weeks or 9 cycles. Subjects on the CIV rhIL-2 arm who achieve both a 25% increase and at least a 100 cell/mm3 increase in CD4 count above the prerandomization baseline value after 3 cycles or after 6 cycles will switch to rhIL-2 at 7.5 MIU by subcutaneous injection twice a day for 5 days every 8 weeks for the remainder of their treatment course. Results and Future Plans: The study is ongoing and treatment arms remain blinded, therefore study conclusions and significance can not yet be discussed. The study is continuing to enroll patients and will continue to do so until national enrollment goals are met. Significance: Improvement in immune function remains an illusive goal for many patients with HIV infection. This study will aid in developing immune restorative therapies for patients with HIV infection.