Mediators of the Relationship Between Depression and HIV Medication Adherence

描述（由申请人提供）：对高效抗逆转录病毒治疗（HAART）的依从性差是HIV治疗和预防中的一个重要临床问题，因为极高水平的HAART依从性是维持病毒抑制所必需的。最近的证据表明，在全国范围内，只有19%接受HAART治疗的患者表现出最佳的依从性并实现病毒的完全抑制。努力更好地了解和改进HAART疗法的依从性对于管理艾滋病毒/艾滋病流行病至关重要。新发艾滋病毒感染负担过重的群体是生活在城市地区的低收入少数群体药物使用者。特别是在华盛顿特区，美国每年报告的新艾滋病毒/艾滋病病例率最高，新感染人数增加最显著的是低收入、少数族裔药物使用者。在这一组中，最显著和最普遍的患者层面障碍之一是抑郁症状。抑郁症状，即使是亚临床水平，也比其他相关的社会心理因素（包括目前的药物使用情况）更能预测不依从。尽管关注于抑郁症状作为艾滋病毒药物使用者HAART不依从性的可靠而有力的预测因素，但很少有研究试图测试这种关系的潜在机制，这是促进我们理解抑郁如何影响依从性的重要一步，从而为这一群体的干预工作提供信息。运用基于强化的理论，我们关注与抑郁和物质使用相关的两个关键的共同行为/环境因素，包括：(1)目标导向活动水平的降低和(2)环境中积极强化的减少。大量证据表明这些因素与HAART依从性相关；然而，它们还没有作为抑郁症状和HAART依从性之间关系的潜在中介进行测试。因此，该提案的目的是在低收入HIV阳性物质使用者样本中测试目标导向活动水平和正强化在这种关系中的中介作用。我们将采用重复测量设计，评估自我报告和临床医生评定的抑郁症状、药物使用、目标导向活动水平、积极强化、HAART依从性以及临床指标（病毒载量、CD4计数），为期3个月。样本将包括从华盛顿特区的一家大型艾滋病毒诊所招募的125名艾滋病毒阳性药物使用者。结果具有重要意义，因为它们将提供第一个潜在机制的测试，可能解释低收入，少数药物使用者中抑郁症和HAART依从性之间的关系，这一群体对艾滋病毒的不良结果具有极高的高风险。正如Kazdin（2007）所指出的，为了最大限度地节约和优化干预措施的功效，确定中介是至关重要的。目前的研究结果对于提高针对抑郁症和HAART依从性的综合干预措施的有效性和经济性具有明确的意义，同时对于预防也具有重要意义，因为更好地了解和提高依从性可能会降低这一高危人群的传播风险。

DESCRIPTION (provided by applicant): Poor adherence to highly active antiretroviral therapy (HAART) is a significant clinical issue in the treatment and prevention of HIV, as extremely high levels of HAART adherence are necessary to maintain viral suppression. Recent evidence suggests only 19% of individuals on HAART nationwide show optimal adherence and achieve full viral suppression. Efforts to better understand and improve HAART adherence are crucial to managing the HIV/AIDS epidemic. A group that evidences a disproportionate burden of new HIV infection is low-income minority substance users living in urban areas. In D.C. specifically, where the highest rate of new HIV/AIDS cases in the U.S. are reported each year, the most notable increase in new infection has been among low-income, minority substance users. In this group, one of the most significant and prevalent patient-level barriers to adherence is depressive symptoms. Depressive symptoms, even at subclinical levels, predict nonadherence above and beyond other relevant psychosocial factors, including current substance use. Despite the focus on depressive symptoms as a reliable and powerful predictor of HAART nonadherence among substance users with HIV, few studies have sought to test potential mechanisms underlying this relationship, which is an important step to advance our understanding of how depression affects adherence to inform intervention efforts in this group. Using reinforcement-based theory, we focus on two key shared behavioral/environmental factors related to both depression and substance use that include: (1) reductions in goal-directed activity level and (2) reductions in positive reinforcement in one's environment. Extensive evidence suggests the relevance of these factors to HAART adherence; however, they have not been tested as potential mediators of the relationship between depressive symptoms and HAART adherence. Thus, the aim of the proposal is to test the mediating roles of goal-directed activity level and positive reinforcement in this relationship in a sample of low-income HIV positive substance users. We will use a repeated measures design assessing self-report and clinician rated measures of depressive symptoms, substance use, goal-directed activity level, positive reinforcement, and HAART adherence, as well as clinical indicators (Viral Load, CD4 count) over a 3-month period. The sample will include 125 HIV positive substance users recruited from a large HIV clinic in Washington, D.C. Results have important implications as they would provide the first test of potential mechanisms that may account for the relationship between depression and HAART adherence among low-income, minority substance users, a group at extremely high-risk for poor HIV outcomes. As Kazdin (2007) noted, it is crucial to identify mediators in order to maximize parsimony and optimize efficacy of interventions. Current findings have clear implications for increasing effectiveness and parsimony of integrated interventions to target depression and HAART adherence, as well as important implications for prevention, as better understanding and improving adherence may reduce the risk of transmission in this high-risk group. PUBLIC HEALTH RELEVANCE: Efforts to better understand and improve adherence to highly active antiretroviral therapy (HAART) among low- income, minority substance users living with HIV is crucial to managing the HIV/AIDS epidemic. One reliable and powerful predictor of nonadherence in this population is depression, yet to date no studies have tested how depression impacts adherence. The goal of the current proposal is to test potential mechanisms of the relationship between depression and HAART nonadherence among low-income HIV positive substance users, which has clear implications for increasing effectiveness and parsimony of existing prevention and treatment interventions.