Effects of HIV, Cocaine, and Prolonged ART Use on Subclinical Cardiovascular Disease

由于抗逆转录病毒治疗的成功，艾滋病毒携带者的年龄一直在稳步上升 (抗逆转录病毒治疗)，以及持续的新感染，美国的艾滋病毒携带者人数现在为120万，而且还在继续 站起来。由于大多数感染艾滋病毒的老年人是在年轻或中年时感染的，从长期来看 艾滋病毒和抗逆转录病毒疗法的影响现在正在显现。艾滋病毒/抗逆转录病毒治疗相关的合并症是 感染艾滋病毒的人。在非感染性合并症中，冠状动脉疾病(CAD)已成为 导致感染艾滋病毒的老年人死亡的主要原因。除了CAD传统的危险因素外，艾滋病毒 而ART，可卡因的使用已被证明与CAD有关。1999年，我们收到了美国国立卫生研究院的第一笔拨款 美国将调查艾滋病毒和可卡因使用对亚临床动脉粥样硬化的影响，特别是艾滋病毒- 相关的心血管合并症。自那时以来，该团队进行了4项由NIDA资助的研究，并进行了 研究参与者的队列，有/没有艾滋病毒感染，有/没有抗逆转录病毒治疗和有/没有使用可卡因，有 已经在马里兰州的巴尔的摩成立并连续17年受到关注。追求审查的目标 艾滋病毒感染、长期接触抗逆转录病毒药物、长期使用可卡因以及 其他因素对亚临床冠心病的影响，我们发现可卡因的使用可以诱发/加速亚临床冠心病和其他 与艾滋病毒相关的合并症。我们最近确定了几个高度优先的研究问题/假设 值得与其他研究人员合作深入探索：(1)冠状动脉斑块体积可能 对量化与冠状动脉斑块负荷相关的因素更敏感，(2)端粒长度可能是 (3)肌钙蛋白T可能是冠脉斑块程度的标志物 同型半胱氨酸可能是艾滋病毒/可卡因相关合并症的潜在有用的生物标志物。 U01的中心目标是进一步研究可卡因的使用是否以及如何影响艾滋病毒/抗逆转录病毒治疗- 相关的冠心病和其他合并症。这项拟议研究的具体目的是：(1)维护和 扩大我们现有的涉及艾滋病毒/抗逆转录病毒药物和可卡因相关心血管疾病和其他共病的队列 作为高优先级研究的平台和其他科学合作的平台； 从纵向上看，艾滋病毒、长期使用可卡因和长期接触抗逆转录病毒药物对存在的影响， CCTA定义的亚临床/临床CAD的发展和进展，(3)调查可卡因是否使用 加剧艾滋病毒感染的可卡因使用者认知功能的下降，(4)调查 HIV和可卡因是否与端粒缩短有关，以及(5)检查相互关系 同型半胱氨酸(Hcy)与艾滋病毒/抗逆转录病毒药物/可卡因相关的共病之间的关系。中提出的所有假设 这一应用尚未经过测试，对艾滋病毒/艾滋病和药物滥用的科学领域至关重要。 拟议的研究将对更好地了解药物滥用是否以及如何滥用做出独特的贡献 加剧艾滋病毒携带者和药物使用障碍者的心血管和其他共病。

As the age of people living with HIV has been rising steadily due to the success of antiretroviral therapy (ART), and continued new infections, the number of people with HIV in the US is now 1.2 million and continues to rise. Since most older adults living with HIV were infected as young adults or in middle age, long-term effects of HIV and ART are now emerging. HIV/ART-associated comorbidities represent a major challenge for HIV-infected individuals. Of noninfectious comorbidities, coronary artery disease (CAD) has become one of leading causes of death among older people with HIV infection. In addition to CAD traditional risk factors, HIV and ART, cocaine use has been shown to be associated with CAD. In 1999, we received the first NIH grant in the US to investigate the effects of HIV and cocaine use on subclinical atherosclerosis, specifically HIV- associated cardiovascular comorbidity. Since then, 4 NIDA-funded studies by this team were conducted and a cohort of study participants, with/without HIV infection, with/without ART and with/without cocaine use, has been established and followed in Baltimore, Maryland for 17 consecutive years. Pursuing the goal of examining the individual and combined effects of HIV infection, long-term exposure to ART, chronic cocaine use, and other factors on subclinical CAD, we found that cocaine use may induce/accelerate subclinical CAD and other HIV-associated comorbidities. We recently identified several high priority research questions/hypotheses that deserve to be explored thorough collaborations with other investigators: (1) coronary plaque volume may be more sensitive to quantify factors associated with coronary plaque burden, (2) telomere length may be associated with HIV, cocaine use and aging, (3) Troponin T may be a maker for the degree of coronary plaque burden, and (4) homocysteine may be a potentially useful biomarker for HIV/cocaine associated comorbidities. The central objective for this U01 is to further examine whether and how cocaine use influences the HIV/ART- associated CAD and other comorbidities. The specific aims of this proposed study are: (1) to maintain and expand our existing cohort involving HIV/ART and cocaine-associated cardiovascular and other comorbidities as a platform for high priority research and as a platform for other scientific collaborations; (2) to examine longitudinally the effects of HIV, chronic cocaine use, and prolonged ART exposure on the presence, development and progression of CCTA-defined subclinical/clinical CAD, (3) to investigate whether cocaine use exacerbates the HIV-associated decline in cognitive function in HIV-infected cocaine users, (4) to investigate whether HIV and cocaine are associated with telomere shortening, and (5) to examine interrelationships between homocysteine (Hcy) and HIV/ART/cocaine-associated comorbidities. All the hypotheses proposed in this application have not been tested and are crucial to the scientific field of HIV/AIDS and substance abuse. The proposed study will make unique contributions to a better understanding of whether and how drug abuse exacerbates cardiovascular and other comorbidities in those with HIV and substance use disorder.