PACTG P1015: INTENSIFICATION OF HIV-SPECIFIC CD4 & CD8 ACTIVITY BY CYCLING HAART

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。PACTG 1015是一项概念验证研究，旨在确定暂停HAART治疗对HIV阳性儿童和青少年CD4和CD8活性的影响，这些儿童和青少年的病毒抑制量< 50 HIV RNA拷贝/ml。据推测，暂停HAART治疗导致HIV病毒血症的短暂和低水平增加可能会促进HIV特异性CD8和CD4 T细胞。在随后重新引入HAART抑制病毒血症后，扩增的CD8群体可能能够更好地控制病毒复制或消除一些细胞相关的HIV。这可能导致更长的病毒血症期，随后暂停HAART治疗。该研究将首先招募4岁至21岁以下的儿童和青少年；在证明该方法在该年龄组的安全性后，队列II将开放并入组bb02和< 4岁的儿童。在每个年龄组中有两组：一组将循环使用和关闭HAART （A组），另一组将继续使用HAART （B组）。B组的受试者是那些没有选择进入A组的受试者。A组的受试者将参与抗病毒药物治疗时间与药物治疗时间（药物假期）交替进行的周期。第一次中断（周期1）将持续三天。每次后续中断将增加两天（周期n+2天）。在药物假期结束时，将测试受试者的病毒载量。在接下来的一周内，受试者在等待病毒载量结果的同时继续进行HAART治疗。如果它仍然低于检测水平，他们将开始下一个周期。如果他们的血浆病毒载量在药物假期结束时可以检测到，他们将进入可检测的病毒周期，并将继续进行28天的抗病毒治疗。任何处于可检测病毒周期的受试者，如果他们能够抑制病毒载量，就会进入下一个药物假期周期。如果他们不能抑制病毒载量，他们继续进行28天的治疗（也称为可检测病毒周期），最多4个周期。如果受试者未能通过四个治疗周期（即在连续HAART治疗112天后仍确认可检测到血浆病毒血症），他们将被取消研究。当病毒载量超过500 cp/ml时进行耐药性检测。未停止治疗的对照组受试者也将接受每三个月常规血浆病毒血症检测以及更高级的免疫和病毒学检测。

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. PACTG 1015 is a proof of concept study to determine the effects of suspending HAART on CD4 and CD8 activity in HIV-positive children and adolescents who have achieved viral suppression of < 50 HIV RNA copies/ml. It is hypothesized that a brief and low level increase in HIV viremia, resulting from suspension of HAART might boost HIV-specific CD8 and CD4 T cells. After the subsequent suppression of viremia with the reintroduction of HAART, the expanded CD8 population might be able to better control viral replication or to eliminate some of the cell-associated HIV. This could result in a more prolonged period of aviremia with a subsequent suspension of HAART. The study will initially enroll children and adolescents > 4 and < 21 years of age; after safety of the approach is demonstrated in this age group, cohhort II will open and enroll children > 2 and < 4 years of age. Within each age cohort there are two groups: one that will cycle on and off HAART (Group A) and a control group that will remain on continuous HAART (Group B). Subjects in Group B will be those who do not choose to enter Group A. Subjects in Group A will participate in cycles that alternate the time on antiviral medication with time off of the medication (drug holiday). The first interruption (cycle 1) will be for three days. Each subsequent interruption will add two days (cycle n+2 days). At the end of the drug holiday, the subjects' viral load will be tested. During the following week, the subjects' resume their HAART therapy while waiting for the viral load results. If it remains below the level of detection, they will begin the next cycle. If their plasma viral load becomes detectable at the end of the drug holiday, they will move to the detectable virus cycle and will remain on antiviral therapy for 28 days. Any subject in a detectable virus cycle is moved to the next drug holiday cycle if they are able to suppress their viral load. If they are not able to suppress their viral load, they remain on the 28-day treatment (also called detectable virus cycle) for a maximum of 4 cycles. If subjects fail four treatment cycles (i.e. they still have a confirmed detectable plasma viremia after 112 days of continuous HAART), they will be taken off study. Resistance testing will be performed when viral load exceeds 500 cp/ml. The control group of subjects who do not undergo discontinuation of their therapy will also be evaluated with routine plasma viremia measured every three months as well as more advanced immunologic and virologic assays.