IV OR SQRHIL2 IN HIV INFECTED SUBJECTS ON HAART

本研究的主要假设是不同途径间歇给予rhIL-2之间存在差异（IV与皮下给药）与单独使用高效抗逆转录病毒治疗相比，在rhIL治疗一年后CD 4计数比随机化前基线值增加50%的受试者比例方面，使用高效抗逆转录病毒治疗方案（IV与皮下给药）-2和CD 4计数的变化率。该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之间是否存在差异，以及当HAART用于rhIL-2时，与单独HAART相比，免疫细胞表型和功能以及HIV病毒载量和抗病毒药物耐药性发展率是否存在可测量的变化。研究方法：这是一项随机化研究，旨在确定在CD 4计数为50- 300个细胞/mm 3的HIV患者中，通过连续静脉输注与皮下注射给予高剂量间歇性rhIL-2联合高效抗逆转录病毒治疗与单独高效抗逆转录病毒治疗对CD 4应答的影响。受试者必须是蛋白酶抑制剂初治者。所有受试者将接受茚地那韦和2种核苷类似物治疗;其中一种是受试者新使用的（HAART）。受试者将接受12周的HAART治疗。在第10周，将由Chiron通过bDNA（真实的时间）进行HIV RNA检测。<5，000拷贝/ml的受试者将继续参加研究。> 5，000拷贝/ml的受试者将不需要进一步随访，并应退出研究。HIV RNA <5，000拷贝/ml的受试者随后将被随机分配继续单独HAART或HAART与rhIL-2，900万单位，每8周一次持续5天，持续72周或9个周期，或rhIL-2，750万单位，每天两次，每8周一次皮下注射持续5天，持续72周或9个周期。CIV rhIL-2组的受试者在3个周期后或6个周期后达到CD 4计数增加25%且高于随机化前基线值至少增加100个细胞/mm 3，将在其治疗过程的剩余时间内转换为皮下注射rhIL-2，剂量为7.5 MIU，每日两次，每8周一次，持续5天。结果和未来计划：该研究正在进行中，治疗组仍保持盲态，因此尚不能讨论研究结论和意义。该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HIV感染患者开发免疫恢复疗法。

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.