Prospective Memory in HIV-1 Infection

描述（由申请人提供）：尽管在联合抗逆转录病毒疗法（cART）时代，坦率痴呆的患病率有所下降，但HIV相关神经认知障碍（HAND）仍然很常见，并继续对健康结果产生负面影响。老年HIV感染者（O+）代表了美国流行病的一个不断增长的亚群，特别容易受到HAND及其对cART依从性和HIV相关残疾的不利影响。然而，目前还没有经过验证的神经心理学治疗方法用于HAND及其功能后果的管理（例如，不遵守）在O+。前瞻性记忆（PM）是一个可行的结构，在此基础上开发新的认知神经康复策略，以改善O+患者HAND的健康结果。PM是认知的一个独特而普遍的方面，它包含了“记住记住”的复杂过程。在先前的补助金期间，我们已经表明，O+在PM的战略方面，这是强烈和独立的预测艾滋病毒相关的残疾，包括失业和cART不遵守赤字的风险。在此基础上，我们修订后的更新申请努力将之前资助期间获得的关于HIV PM的观察知识转化为O+中HAND的有效，理论驱动，基于PM的干预。具体来说，这种更新将确定在有影响力的多过程理论（McDaniel & Einstein，2000）的指导下增强PM的战略方面是否会改善实验室和日常生活中的PM（即，自然主义任务）。研究目标将在200名O+和50名人口统计学上相当的血清阴性参与者（O-）中进行评估，他们将在UCSD HIV神经行为研究计划（HNRP）接受全面的医学，精神病学和神经认知评估。所有参与者将接受一系列平行的实验室和自然主义实验，旨在验证这一假设，即支持战略处理将显着提高（和“正常化”）PM性能O+。这个修订后的应用程序响应的初步审查，提供了可行性数据的自然PM实验，增加了日常干预事件和记忆策略的措施，并澄清了一些理论和后勤问题。该研究的翻译性质也将使我们能够确定通过支持实验室中O+之间的策略处理获得的PM益处的大小是否与相同个体中自然环境中的平行响应相关。这些以治疗为重点的实验研究的结果预计将作为后续I期临床试验的跳板。因此，该更新申请代表了将基于观察性队列的发现转化为HAND的新治疗方法的关键翻译sep，该方法可能改善O+患者的健康结局。

DESCRIPTION (provided by applicant): Although the prevalence of frank dementia has decreased in the era of combination antiretroviral therapies (cART), HIV-associated neurocognitive disorders (HAND) remain common and continue to negatively impact health outcomes. Older HIV-infected adults (O+) represent a growing subpopulation of the U.S. epidemic that is especially vulnerable to HAND and its adverse impact on cART adherence and HIV-related disability. Yet there are presently no neuropsychological treatments validated for management of HAND and its functional consequences (e.g., non-adherence) in O+. Prospective memory (PM) is a viable construct upon which to develop novel cognitive neurorehabilitation strategies to improve health outcomes in HAND among O+. PM is a unique and ubiquitous aspect of cognition that encompasses the complex process of "remembering to remember". Over the prior grant periods we have shown that O+ are at particular risk of deficits in the strategic aspects of PM, which are strongly and independently predictive of HIV-related disability, including unemployment and cART non-adherence. Building on this foundation, our revised renewal application endeavors to translate the observational knowledge gained about PM in HIV from the prior funding period into an effective, theory-driven, PM-based intervention for HAND among O+. Specifically, this renewal will determine whether enhancing the strategic aspects of PM as guided by the influential Multiprocess Theory (McDaniel & Einstein, 2000) improves PM in the laboratory and in daily life (i.e., a naturalistic task). Study aims will be evaluated in 200 O+ and 50 demographically comparable seronegative participants (O-), who will receive a comprehensive medical, psychiatric, and neurocognitive assessment at the UCSD HIV Neurobehavioral Research Program (HNRP). All participants will undergo a series of parallel laboratory and naturalistic experiments designed to test the hypothesis that bolstering strategic processing will significantly improve (and "normalize") PM performance among O+. This revised application responds to the initial review by providing feasibility data for the naturalistic PM experiments, adding measures of daily intervening events and memory strategies, and clarifying several theoretical and logistical issues. The translational nature of tis study will also allow us to determine whether the magnitude of the PM benefits gained through supporting strategic processing among O+ in the laboratory are associated with a parallel response in the naturalistic setting in the same individuals. Findings from these treatment-focused experimental investigations are expected to serve as a springboard for a subsequent Phase I clinical trial. Accordingly, this renewal application represents a critical translational sep in converting observational cohort-based findings into novel treatments for HAND that may improve health outcomes among O+.