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

由于抗逆转录病毒疗法的成功，艾滋病毒感染者的年龄一直在稳步上升， (ART)，以及持续的新感染，美国艾滋病毒感染者人数现在为120万， 上升。由于大多数感染艾滋病毒的老年人是在年轻人或中年时感染的， 艾滋病毒和抗逆转录病毒疗法的影响正在显现。艾滋病毒/抗逆转录病毒治疗相关的合并症是一个重大挑战， 艾滋病毒感染者。在非感染性合并症中，冠状动脉疾病（CAD）已成为 这是感染艾滋病毒的老年人死亡的主要原因。除了CAD的传统风险因素， 和抗逆转录病毒疗法，可卡因的使用已被证明与CAD有关。1999年，我们获得了第一笔NIH拨款。 美国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- 相关心血管并发症。从那时起，该团队进行了4项NIDA资助的研究， 一组研究参与者，有/无艾滋病毒感染，有/无抗逆转录病毒治疗，有/无可卡因使用， 在马里兰州的巴尔的摩成立并连续17年受到关注。追求的目标是检查 艾滋病毒感染、长期接触抗逆转录病毒疗法、长期使用可卡因和 我们发现，可卡因的使用可能会诱发/加速亚临床CAD和其他 HIV相关合并症。我们最近确定了几个高优先级的研究问题/假设， 值得与其他研究者深入合作探讨：（1）冠状动脉斑块体积可能是 对冠状动脉斑块负荷相关的量化因素更敏感，（2）端粒长度可能是 与HIV、可卡因使用和年龄相关;（3）肌钙蛋白T可能是冠状动脉斑块程度的标志物 高半胱氨酸可能是HIV/可卡因相关共病的潜在有用生物标志物。 U 01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/抗逆转录病毒疗法， 相关CAD和其他合并症。本研究的具体目标是：（1）保持和 扩大我们现有的队列，包括HIV/ART和可卡因相关的心血管疾病和其他合并症 作为高优先级研究的平台和其他科学合作的平台;（2）检查 纵向的影响，艾滋病毒，慢性可卡因的使用，和长期的ART暴露的存在， CTA定义的亚临床/临床CAD的发展和进展，（3）研究可卡因使用是否 加剧HIV感染可卡因使用者的HIV相关认知功能下降，（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HIV/ART/可卡因相关共病之间的关系。所有的假设都是在 这种应用还没有经过测试，对艾滋病毒/艾滋病和药物滥用的科学领域至关重要。 拟议的研究将为更好地了解药物滥用是否以及如何 加重HIV和物质使用障碍患者的心血管和其他合并症。

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.