HIV AND COCAINE USE--CARDIOVASCULAR EFFECTS AND THERAPY

拟议的研究是根据RFA HL-98-012的要求制定的，RFA HL-98-012要求申请调查艾滋病毒感染中可卡因滥用引起的心血管并发症，重点是呼吁进行临床研究以确定有效的治疗方案。艾滋病毒阳性个体使用可卡因是未感染个体的主要感染媒介，也可能对疾病进展产生不利影响，包括增加心血管功能障碍的风险。因此，同时针对可卡因使用和心血管疾病的治疗方法对艾滋病毒阳性、可卡因滥用患者群体极为有益。拟议的研究利用血管紧张素转换酶（ACE）抑制剂fosinopril在许多组织系统中的多重作用，并将研究其通过大脑活动减少可卡因使用的能力，以及通过对心脏和心血管系统的作用（包括血小板聚集因子）逆转或预防可卡因和HIV疾病的心脏毒性作用的能力。在这项拟议的5年研究中，124名HIV阳性的可卡因依赖美沙酮维持的患者将被随机分配接受福sinopril （20mg /天）或安慰剂治疗6个月。本研究的具体目的是：(a)基于每周两次的尿液毒理学筛查，调查福sinopril治疗艾滋病毒阳性美沙酮维持患者可卡因依赖的疗效；(b)通过比较治疗前后的二维超声心动图和多普勒超声心动图来确定福辛普利改善心脏功能的能力，(c)研究福辛普利降低血小板对生理激动剂反应性的能力。还将检查心血管疾病的生物和社会心理风险因素（包括CD4计数、病毒载量、抗逆转录病毒药物、心血管疾病家族史、成瘾严重程度、抑郁和可卡因使用期间的主观心血管窘迫）。

The proposed study was formulated in response to RFA HL-98-012 requesting applications to investigate cardiovascular complications from cocaine abuse in HIV infection, with a focus on the call for clinical studies to identify effective treatment protocols. Cocaine use by HIV-positive individuals represents a primary vector of infection to non-infected individuals, and may also adversely affect disease progression, including increasing risk for cardiovascular dysfunction. A treatment approach targeting both cocaine use and cardiovascular disorders simultaneously would therefore be extremely beneficial in an HIV- positive, cocaine-abusing patient population. The proposed study capitalizes on the multiple effects of the angiotensin converting enzyme (ACE) inhibitor, fosinopril, in numerous tissue systems, and will investigate its ability to reduce cocaine use through activity in the brain, and to reverse or prevent the cardiotoxic effects of cocaine and HIV disease by actions upon the heart and cardiovascular system, including platelet aggregation factors. In the proposed five-year study, one hundred and twenty-four HIV- positive cocaine-dependent methadone-maintained patients will be randomly assigned to receive either fosinopril (20 mg/day) or placebo for six months. The specific aims of this study are: (a) to investigate the efficacy of fosinopril for the treatment of cocaine dependence in HIV-positive methadone-maintained patients, based on twice weekly urine toxicology screens; (b) to determine the ability of fosinopril to improve cardiac functioning by comparing pre- and post-treatment two-dimensional and Doppler echocardiograms, and (c) to investigate the ability of fosinopril to decrease platelet reactivity to physiological agonists. Biological and psychosocial risk factors for cardiovascular disorders (including CD4 count, viral load, antiretroviral medications, family history of cardiovascular disease, severity of addiction, depression, and subjective cardiovascular distress during cocaine use) will also be examined.