PHASE II, RANDOMIZED, DOUBLE-BLIND STUDY OF THE SAFETY AND EFFICACY OF SCH 41

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 具体目标 主要目的 在当前含利托那韦的抗逆转录病毒治疗方案失败的HIV感染、经治受试者中评价3种剂量水平SCH 417690在14天内的病毒学活性。 次要目的 ¿ 评估SCH 417690的长期安全性和耐受性。 ¿ 评价SCH 417690 3次给药联合基于基线基因型和表型检测优化的含利托那韦的抗逆转录病毒背景治疗方案在24周和48周时的病毒学活性。 ¿ 为了评估筛选患者群体中的基线辅助受体向性表型，辅助受体表型（即，从检出仅CCR 5病毒到检出CCR 5/CXCR 4或仅CXCR 4病毒），以及X4病毒株作为少数准种是否影响SCH 417690的病毒学应答。 ¿ 探索接受SCH 417690治疗的病毒学失败受试者对SCH 417690和背景抗逆转录病毒方案的敏感性变化以及病毒适应度变化。 ¿ 在接受SCH 417690的受试者中，探索既往和/或当前使用恩夫韦肽对病毒学应答的影响。 ¿ 评价SCH 417690联合优化的背景含利托那韦抗逆转录病毒方案治疗24周和48周时的免疫活性。 ¿ 探索SCH 417690对免疫系统应答和临床感染性疾病发生率的影响。 ¿ 探索第14天和第8周SCH 417690浓度分别与第4周和第24周（或提前终止研究药物）病毒学应答的关系。 ¿ 探索SCH 417690和背景抗逆转录病毒药物依从性与病毒学应答的关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS Primary Objective To evaluate the virologic activity over 14 days of three dose levels of SCH 417690 in HIV-infected, treatment-experienced subjects who are failing their current ritonavir-containing antiretroviral regimen. Secondary Objectives ¿ To assess the longer-term safety and tolerability of SCH 417690. ¿ To evaluate the virologic activity at 24 and 48 weeks of three doses of SCH 417690 together with a background ritonavir-containing antiretroviral regimen optimized on the basis of baseline genotypic and phenotypic testing. ¿ To assess baseline coreceptor tropism phenotype in the screening patient population, changes in coreceptor phenotype (i.e., from detection of CCR5-only virus to detection of CCR5/CXCR4 or to CXCR4-only virus) in subjects taking SCH 417690, and whether the presence of X4 viral strains as a minority quasi-species influences the virologic response to SCH 417690. ¿ To explore change in susceptibility to SCH 417690 and the background antiretroviral regimen, and changes in viral fitness in subjects receiving SCH 417690 who experience virologic failure. ¿ To explore the effect of past and/or current enfuvirtide use on virologic response in subjects receiving SCH 417690. ¿ To evaluate the immunologic activity at 24 and 48 weeks of SCH 417690 together with an optimized background ritonavir-containing antiretroviral regimen. ¿ To explore the effects of SCH 417690 on immune system responses and the incidence of clinical infectious diseases. ¿ To explore the relationship of SCH 417690 concentrations at Day 14 and Week 8 to virologic response at Week 4 and at Week 24 (or earlier study drug termination), respectively. ¿ To explore the relationship of adherence with SCH 417690 and background antiretrovirals to virologic response.